Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Metabolic profile of Phellodendron amurense Rupr. in vivo of rat and its metabolomic study on intervention in rheumatoid arthritis.

To analyze the metabolites (blood, urine and feces) in normal rats after intragastric administration of the decoction of Phellodendri Amurensis Cortex (PAC) and to map the metabolic profile of PAC in vivo of rat; meanwhile, to evaluate the anti-rheumatoid arthritis (RA) effect of PAC by blood metabolomics technique and to explore its mechanism. Performing on UPLC-Q-TOF-MS technology with a Waters ACQUITY UPLC BEH-C18 column (100 mm × 2.1 mm, 1.7 µm), the mobile phase was acetonitrile-0.1% formic acid aqueous solution (gradient elution). Prior to and following the administration of the decoction of PAC, the samples of blood, urine, and fecal were collected from the rats, in the positive ion mode, pharmacogenic metabolites in each biological sample were identified according to the accurate mass, fragment ions, retention time, metabolic reaction type, comparison of reference substance and retrieval of Pub Med database; The adjuvant-type arthritis (AA) rat model was established, and blood metabonomics method was used to study the improvement effect of rheumatoid arthritis after drug intervention with PAC, and its mechanism was preliminarily explored through analysis of metabolic pathway. A total of 72 exogenous components were identified, including 17 prototype components and 55 metabolites; 14 biomarkers were screened by blood metabolomics techniques combined with multivariate statistical analysis, and PAC significantly improved symptoms of rheumatoid arthritis in rats, and the metabolic pathway analysis mainly involves 5 metabolic pathways. The components in the aqueous decoction of PAC mainly undergo phase I metabolic reactions in rats, such as oxidation, reduction, dehydrogenation, demethylation, and phase II metabolic reactions, such as acetylation, glucuronidation, methylation; PAC has anti-rheumatoid arthritis effects, and its mechanism of action may be related to biosynthesis of aminoacyl-tRNA, metabolism of phenylalanine, metabolism of tryptophan, degradation of valine, leucine and isoleucine and biosynthesis of pantothenic acid and coenzyme A, providing a scientific basis for the study of the pharmacodynamic substances and the action mechanism of PAC against RA.

Protocol of the development of a core outcome set for stroke in multidimensional value assessment of traditional Chinese medicine.

INTRODUCTION: Stroke is the most common cause of death in China. In Chinese clinical practise, traditional Chinese medicine (TCM) and integrative medicine have been widely used as adjuvant therapies for the treatment of stroke. However, their clinical effectiveness, particularly their clinical value, has been inconsistent in the literature mainly because various outcome measures have been used and reported in clinical research. Hence, obtaining a comprehensive list of outcomes for TCM value assessment is crucial for a multidimensional value assessment. Therefore, the main objective of this protocol was to develop an outcome set used in health technology assessment (HTA) decision-making for TCM treatment of stroke. METHODS AND ANALYSIS: The outcome set will be developed in four phases: (1) we will perform a systematic literature review to identify candidate outcomes that have been previously measured in published studies; (2) we will develop a comprehensive list of outcome measures by conducting a multistakeholder semistructured interview; (3) we will conduct two-round Delphi surveys to prioritise outcomes for each HTA domain; and (4) we will finalise the outcome sets by holding a ratification meeting with multiple stakeholder groups. The developed outcome set should be measured and reported as the minimum set of outcomes for HTA assessment for the TCM treatment of acute ischaemic stroke (AIS). ETHICS AND DISSEMINATION: This protocol was reviewed and approved by the Institutional Review Board of the Minhang Hospital of Fudan University. Our findings will be shared at academic conferences and in peer-reviewed publications.

Study on chemical constituents and fingerprints of Phellodendron amurense Rupr. based on ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry.

The chemical constituents from Phellodendron amurense Rupr. were characterized systematically by ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry method for collecting mass spectrometry data, and the fingerprints method was established, providing reference for its quality control. The chromatographic column was ACQUITY UPLC BEH-C18 (100 mm×2.1 mm, 1.7 µm). The mobile phase was acetonitrile-0.1% formic acid aqueous solution and the compounds from P. amurense Rupr. were identified by Qualitative Analysis 10.0 software, reference substance, retention time, mass spectrometry fragmentation pattern and database retrieval. Meanwhile, liquid chromatography-mass spectrometry fingerprint methods of P. amurense Rupr. and Phellodendron chinense Schneid. were established by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine (2012 edition), and the differences were analyzed by multivariate statistical analysis methods. A total of 105 compounds were identified, including 102 alkaloids, two phenolic acids, and one lactone compound. Liquid chromatography-mass spectrometry fingerprint method was established with ideal precision, stability and repeatability, and 12 quality differential markers were recognized between the above two herbs. Liquid chromatography-mass spectrometry method can be used for qualitative analysis of the constituents of Phellodendron amurense Rupr., providing reference for clarifying the material basis and promoting the clinical precision medication and quality evaluation of P. amurense Rupr.

[Characteristics, origin, and processing of Poria in Qing Dynasty Palace:evidence of both historical relics and documents].

Poria(Fu Ling) is a bulk traditional Chinese medicine(TCM)with a long history and complex varieties. The royal medical records of the Qing Dynasty include multiple medicinal materials of Fu Ling, such as Bai Fu Ling(white Poria), Chi Fu Ling(rubra Poria), and Zhu Fu Ling(Poria processed with cinnabaris). The Palace Museum preserves 6 kinds of specimens including Fu Ling Ge(dried Poria), Bai Fu Ling, Chi Fu Ling, Zhu Fu Ling, Bai Fu Shen(white Poria cum Radix Pini), and Fu Shen Mu(Poria cum Radix Pini). After trait identification and textual research, we found that Fu Ling Ge was an intact sclerotium, which was processed into Fu Ling Pi(Poriae Cutis), Bai Fu Ling and other medicinal materials in the Palace. The Fu Ling in the Qing Dynasty Pa-lace was mainly from the tribute paid of the officials in Yunnan-Guizhou region. The tribute situation was stable in the whole Qing Dynasty, and changed in the late Qing Dynasty. The cultural relics of Fu Ling in the Qing Dynasty Palace confirm with the archival documents such as the royal medical records and herbal medicine books, providing precious historical materials for understanding Fu Ling in the Qing Dynasty and a basis for the restoration of the processing of the Fu Ling in the Qing Dynasty Palace.

Inspiratory muscle training improves cardiopulmonary function in patients after transcatheter aortic valve replacement: a randomized clinical trial.

AIMS: Inspiratory muscle training (IMT) can increase the strength or endurance of the diaphragm and accessory muscles of inspiration, yet there is no evidence that endorses the role of IMT in patients of transcatheter aortic valve replacement (TAVR). This study for the first time tested the effects of IMT plus usual cardiac rehabilitation (CR) function in patients after TAVR. METHODS AND RESULTS: A double-blinded, randomized controlled, single-centre clinical trial was undertaken. Participants who had a confirmed diagnosis of valve heart disease and were clinically stable after TAVR were recruited and received a CR programme during the hospital stay. A total of 96 patients were recruited and randomly assigned to the IMT + CR group (n = 48) or the CR group (n = 48) in a 1:1 ratio. The group difference in the primary outcome, the 6-min walk distance at the discharge of the hospital, significantly favoured the IMT + CR group (mean difference -33.52, 95% CI: -64.42 to -2.62, P = 0.034). The significant difference was maintained at the 1-month and 3-month follow-ups (mean difference: 41.51, 95% CI: 1.82-81.21, P = 0.041). In addition, the mean hospital stays of subjects in the IMT + CR group was 11 days, which was significantly shorter than the 12.5 days in the CR group (P = 0.016). Sensitivity analysis using per-protocol analysis supported these findings. No adverse treatment-related events were reported. CONCLUSION: Compared with usual CR, IMT plus CR can effectively improve exercise endurance, pulmonary ventilation function, and inspiratory muscle strength in patients after TAVR and shorten the length of hospital stay.

Characteristics, origin, and processing of Poria in Qing Dynasty Palace:evidence of both historical relics and documents / 中国中药杂志

Poria(Fu Ling) is a bulk traditional Chinese medicine(TCM)with a long history and complex varieties. The royal medical records of the Qing Dynasty include multiple medicinal materials of Fu Ling, such as Bai Fu Ling(white Poria), Chi Fu Ling(rubra Poria), and Zhu Fu Ling(Poria processed with cinnabaris). The Palace Museum preserves 6 kinds of specimens including Fu Ling Ge(dried Poria), Bai Fu Ling, Chi Fu Ling, Zhu Fu Ling, Bai Fu Shen(white Poria cum Radix Pini), and Fu Shen Mu(Poria cum Radix Pini). After trait identification and textual research, we found that Fu Ling Ge was an intact sclerotium, which was processed into Fu Ling Pi(Poriae Cutis), Bai Fu Ling and other medicinal materials in the Palace. The Fu Ling in the Qing Dynasty Pa-lace was mainly from the tribute paid of the officials in Yunnan-Guizhou region. The tribute situation was stable in the whole Qing Dynasty, and changed in the late Qing Dynasty. The cultural relics of Fu Ling in the Qing Dynasty Palace confirm with the archival documents such as the royal medical records and herbal medicine books, providing precious historical materials for understanding Fu Ling in the Qing Dynasty and a basis for the restoration of the processing of the Fu Ling in the Qing Dynasty Palace.

[Effect of electroacupuncture on visceral sensitivity and colonic NGF, TrkA, TRPV1 expression in IBS-D rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) on mental state, visceral sensitivity and protein expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and transient receptor potential vanilloid 1 (TRPV1) of colonic tissue in diarrhea-predominant irritable bowel syndrome (IBS-D) rats, and to explore its possible mechanism on treating IBS-D. METHODS: A total of 36 male SD rats of SPF grade were randomized into a blank group, a model group, an EA group and a western medication group, 9 rats in each group. In the model group, the EA group and the western medication group, IBS-D model was established by enema of dinitrobenzene sulfonic acid (DNBS) combined with chronic restraint stress method. In the EA group, EA was applied at "Tianshu" (ST 25) and "Shangjuxu" (ST 37), with disperse-dense wave, in frequency of 2 Hz/100 Hz, 20 min each time, once a day for 7 days. In the western medication group, pinaverium bromide suspension was given by gavage (15 mg•kg-1•d-1) for 7 days. Before and after model establishment, and after intervention, the body mass, 24 h food intake and fecal water content were observed, the visceral sensitivity was detected by abdominal withdrawal reflex (AWR); after intervention, the mental state was evaluated by elevated plus maze (EPM) test, the protein expression of NGF, TrkA and TRPV1 was detected by immunohistochemistry and Western blot in the 4 groups. RESULTS: After model establishment, compared with the blank group, the body mass and 24 h food intake were decreased (P<0.05), first systolic latency of AWR was shortened and number of contraction wave of AWR was increased (P<0.05), and fecal water content was increased (P<0.05) in the model group, the EA group and the western medication group. After intervention, compared with the blank group, open arm residence time ratio (OT%) of EPM was decreased (P<0.05) and protein expression of NGF, TrkA, TRPV1 in colonic tissue was increased in the model group (P<0.05); compared with the model group, the body mass and 24 h food intake were increased (P<0.05), first systolic latency of AWR was lengthened and number of contraction wave of AWR was decreased (P<0.05), the fecal water content was decreased (P<0.05), OT% of EPM was increased (P<0.05), and protein expression of NGF, TrkA, TRPV1 in colonic tissue was decreased (P<0.05) in the EA group and the western medication group. CONCLUSION: Electroacupuncture at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) can relieve the anxiety and depression-like behaviors in IBS-D rats, down-regulate the protein expression of NGF, TrkA, TRPV1 in colonic tissue, so as to reduce the visceral sensitivity and relieve symptoms.

Nephropathy 1st inhibits renal fibrosis by activating the PPARγ signaling pathway.

Renal fibrosis is a manifestation of kidney injury. Nephropathy 1st is a traditional Chinese herbal medicine that has been used as a therapy for kidney disease, but the underlying mechanisms remain elusive. The aim of this study was to investigate the role and underlying mechanisms of Nephropathy 1st on the progression of kidney disease. In the present study, unilateral ureteral obstruction was performed to establish the renal fibrosis rat model. By hematoxylin-eosin staining and immunohistochemical staining analysis, the severity of renal fibrosis was evaluated in vivo. Serum creatinine (CREA) and urea nitrogen (BUN) were measured by ELISA. The expression levels of Col-I, FN, PPARγ, and Klotho were measured by Western blot in rat NRK-49F cells and in fibrotic rats. GW9662 was used to inhibit PPARγ signaling. Metabonomic analysis showed metabolic differences among groups. Nephropathy 1st administration alleviated the progression of rat renal fibrosis and reduced serum creatinine (Scr) and BUN levels. Mechanistically, Nephropathy 1st promoted the expression of PPARγ and thus activated PPARγ signaling, thereby reducing the pro-fibrotic phenotypes of fibroblasts. The therapeutic effect of Nephropathy 1st was abrogated by the PPARγ inhibitor GW9662. Moreover, Nephropathy 1st normalized the dysregulated lipid metabolism in renal fibrosis rats. In conclusion, Nephropathy 1st alleviates renal fibrosis development in a PPARγ-dependent manner.

How does workplace event criticality spur employees' proactivity? The roles of work engagement and mindfulness.

This paper aims to generate insights about whether, how, and when workplace event criticality spurs employee proactivity. We conducted multilevel analyses with a three-wave time-lagged survey of 179 employees and their 55 direct leaders in China to test our proposed model. The findings indicate that workplace event criticality is conducive to stimulating proactive work behavior through improving employee engagement. Further, employee mindfulness amplifies the positive relationship between workplace event criticality and work engagement. Despite the increasingly unavoidable influence of events in the workplace on employee proactivity, empirical research around the relationship and its underlying mechanism has been rather sparse. Our event-oriented research advances this knowledge by unpacking the salient motivating role of workplace events' criticality in employee work engagement and proactivity. It also increases our understanding by illustrating that employee mindfulness will amplify and intensify the motivational potential of workplace event criticality for work engagement.

[Effect of electroacupuncture on colonic motility and RhoA and ROCK protein expression in IBS-D rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Tianshu"(ST25) and "Shangjuxu"(ST37)on gastrointestinal motility, psychological abnormality and expression of RhoA and ROCK protein in rats with diarrhea predominant irritable bowel syndrome (IBS-D), so as to explore its underlying mechanism in improving IBS-D. METHODS: Thirty-six male rats were randomly and equally divided into control, model, EA and medication groups (n=9 in each group). The IBS-D model with psychological abnormality was established by gavage of dinitrobenzene sulfonic acid (DNBS) + chronic restraint stress. EA (2 Hz/100 Hz, 0.3 mA) was applied to bilateral ST25 and ST37 for 20 min, once a day for 7 days. Rats of the medication group received gavage of pinaverium bromide solution (15 mg/kg), once a day for 7 days. The rats' food intake in 24 h, body mass and colonic contraction waves were recorded. The anhedonia-related behavior was measured using the sucrose consumption test. The elevated plus maze test (the open-arm residence time ratio) was used to assess the anxiety-like behavior. The small intestinal propulsion rate test was used to assess the intestinal motility. The expression levels of RhoA and ROCK proteins in the colonic tissue were measured by Western blot. RESULTS: After modeling, the body mass, food consumption, sucrose preference index, the open-arm residence time ratio andlatency of colonic contraction waves were significantly decreased (P<0.05), and the number of contraction waves, intestinal propulsive rate, and the expression levels of RhoA and ROCK proteins considerably increased (P<0.01，P<0.05) in the model group relevant to the control group. Following the interventions, the decrease of body mass, food consumption, sucrose preference index, open-arm residence time ratio and latency of contraction waves, and the increase of the contraction waves, intestinal propulsive rate, and the expression levels of RhoA and ROCK proteins were all reversed by both EA and medication (P<0.05，P<0.01). The effect of EA was significantly superior to that of medication in increasing the sucrose pre-ference index (P<0.05). CONCLUSION: EA can improve both colonic motility and psychological disorders in IBS-D rats with psychological disorder, which may be related to its function in down-regulating the expression of colonic RhoA and ROCK proteins.

Advantages of Small Incision Surgery in Thyroid Tumors.

Objective: Thyroid tumor is a common thyroid disease, and the incidence of complications after traditional thyroid surgery is high, which seriously affects the prognosis of patients. With the development of minimally invasive techniques, small incision surgery has a positive impact on changing the traditional thyroid surgery treatment. However, the gap between small incision surgery and traditional thyroid surgery is unclear, so this meta-analysis was used to evaluate its application value. Methods: Searching English biomedical databases, including PubMed and Science Network and Chinese major biomedical databases, including CNKI, Wanfang, and Weipu. The keywords of the searched articles are as follows: small incision surgery, traditional thyroid surgery, thyroid tumor treatment, clinical efficacy of thyroid tumor, and surgical treatment, and these keywords are searched individually or in combination to track relevant systematic reviews and literature meta-analysis, and conduct other studies. The retrieval period is from the establishment of the database to January 2022. After extracting the article data, the patients were divided into small incision surgery group and traditional thyroid surgery group due to different intervention methods. The Cochrane risk of bias tool was used to assess the quality of the included literature, and RevMan 5.30 was used for meta-analysis. Results: A total of 9 articles met the inclusion criteria. There were 369 patients with small incision surgery and 364 patients with traditional thyroid surgery. Compared with traditional thyroid surgery, patients treated with small incision surgery had significant short hospitalization time (MD -2.72, 95% CI (-3.32, -2.12)), less amount of bleeding (MD -15.52, 95% CI (-20.40, -10.65)), short incision length (MD -12.73, 95% CI (-16.29, -9.17)), lower VAS score (MD -2.58, 95% CI (-4.08, -1.08)), and less complications (RR 0.30, 95% CI (0.21, 0.44)). Conclusion: Compared with traditional thyroid surgery, the results show that small incision surgery can shorten the hospital stay of patients with thyroid tumor, reduce the length of incision, reduce the amount of bleeding and the occurrence of complications, reduce postoperative pain, and have a positive effect on postoperative survival of patients.

Protective effect of valerian extract capsule (VEC) on ethanol- and indomethacin-induced gastric mucosa injury and ameliorative effect of VEC on gastrointestinal motility disorder.

CONTEXT: Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases. OBJECTIVE: To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases. MATERIALS AND METHODS: Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01-1 mg/mL) on ACh/BaCl2-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248-992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice. RESULTS: Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p < 0.01; PGI2 p < 0.05;), along with the alleviation of the levels of MPO (ethanol: 15.56 ± 0.82 vs. 12.15 ± 2.60, p < 0.01; indomethacin: 9.65 ± 3.06 vs. 6.36 ± 2.43, p < 0.05), MDA (ethanol: 1.66 ± 0.44 vs. 0.81 ± 0.58, p < 0.01; indomethacin: 1.71 ± 0.87 vs. 1.09 ± 0.43, p < 0.05), and inflammatory mediators. VEC decreased the high tone induced by ACh/BaCl2 and promoted intestinal transit in normal and neostigmine/adrenaline-induced mice. DISCUSSION AND CONCLUSIONS: VEC showed a potential gastroprotective effect, suggesting that VEC is a promising phytomedicine for the treatment of GI diseases.

Association of sirtuins (SIRT1-7) with lung and intestinal diseases.

"Exterior-interior correlation between the lung and large intestine" is one of the important contents of traditional Chinese medicine. This theory describes the role of the lung and the intestine in association with disease treatment. The "lung-gut" axis is a modern extension of the "exterior-interior correlation between lung and large intestine" theory in TCM. Sirtuin (SIRT) is a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme family with deacetylase properties, which is highly conserved from bacteria to humans. The sirtuin defines seven silencing regulatory proteins (SIRT1-7) in human cells. It can regulate aging, metabolism, and certain diseases. Current studies have shown that sirtuins have dual characteristics, acting as both tumor promoters and tumor inhibitors in cancers. This paper provides a comparative summary of the roles of SIRT1-7 in the intestine and lung (both inflammatory diseases and tumors), and the promoter/suppressor effects of targeting SIRT family microRNAs and modulators of inflammation or tumors. Sirtuins have great potential as drug targets for the treatment of intestinal and respiratory diseases. Meanwhile, it may provide new ideas of future drug target research.

Black phosphorus-Au-thiosugar nanosheets mediated photothermal induced anti-tumor effect enhancement by promoting infiltration of NK cells in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous cancer required combination therapy, such as photothermal therapy and chemotherapy. In recent years, cancer immunotherapies are rapidly evolving and are some of the most promising avenues to approach malignancies. Thus, the combination of the traditional therapies and immunotherapy in one platform may improve the efficacy for HCC treatment. RESULTS: In this work, we have prepared a black phosphorus (BP)-Au-thiosugar nanosheets (BATNS), in which Au-thiosugar coating and functionalization improved the stability of both black phosphorus nanosheets (BPNS) and gold ions in different simulated physiological environments. The compression of the BATNS band gap can convert more photon energy to heat generation compared with BPNS, resulting in higher photothermal conversion efficiency. The in vitro and in vivo results also revealed a stronger reduction on the hepatocellular carcinoma of mice and prolonged survival of disease models compared with BPNS. More importantly, BATNS showed an additional immune effect by increasing local NK cell infiltration but not T cell on the liver cancer treatment, and this immune effect was caused by the thermal effect of BATNS photothermal treatment. CONCLUSIONS: The novel BATNS could improve the stability of BPNS and simultaneously combine the cancer thermotherapy and immunotherapy leaded by local NK cell infiltration, resulting in a better therapeutic efficacy on hepatocellular carcinoma. This work also provided a new path to design BP-based materials for biomedical applications.

Glycyrrhetinic acid reverses antibiotic-induced intestinal epithelial injury through RNA-binding protein human antigen R (HuR).

BACKGROUND: The application/abuse of antibiotics can cause antibiotic-induced intestinal injury (AIJ), a typical clinical issue that disturbs intestinal homeostasis. However, the underlying post-transcriptional mechanism of AIJ remains unknown. Glycyrrhetinic acid (GA) is one of the main components of Glycyrrhiza uralensis Fisch. and Glycyrrhiza inflata Batalin (Fabaceae), and findings of our previous study showed that GA can maintain intestinal homeostasis post-transcriptionally through the RNA-binding protein human antigen R (HuR). PURPOSE: This study aimed to elucidate the role of HuR in AIJ and the protective effects of GA on AIJ. STUDY DESIGN AND METHODS: Clindamycin hydrochloride was used to clarify the effect of the antibiotic on the intestinal epithelium. Intestinal epithelium cell-6 (IEC-6) and Caco2 cells were used to demonstrate the in vitro effects of the antibiotic and GA on intestinal cells. HuR plasmid and siRNA were used to overexpress or silence HuR in vitro. SD rats were induced by using clindamycin hydrochloride capsules (250 mg/kg i.g.) for 7 consecutive days to construct the in vivo AIJ model. Rats of the AIJ model group were administrated GA (10 and 20 mg/kg i.g.) for 7 days, and subsequently, the protective effect of GA on the intestinal epithelium was evaluated. RESULTS: In vitro results showed that the antibiotic (150-500 µM) suppressed proliferation, induced a delay in restitution after wounding, and caused cell cycle arrest at the G0/G1 phase in IEC-6 and Caco-2 cells. Moreover, the expression levels of HuR and its downstream gene, occludin and cyclin D1, decreased after treatment with the antibiotic (500 µM). Overexpression of HuR and GA (10 and 20 µM) reversed the antibiotic-induced inhibition of proliferation and G0/G1 phase arrest, and the antibiotic-induced decrease in HuR, occludin, and cyclin D1 expression was reversed after GA treatment (10 and 20 µM) in IEC-6 cells. In vivo results revealed the antibiotic-induced epithelial injury of both the small intestines (shortened and spared mucosa) and the large intestines (injured/deformed glands, reduced number of cup cells, and evident inflammatory cell infiltration), all of which were ameliorated after GA treatment (10 and 20 µM). CONCLUSION: Antibiotics induce intestinal epithelial injury through HuR, and GA can exert a protective effect on AIJ by restoring HuR levels.

[Effect of Mailuo Shutong Pills in treatment of ischemic stroke based on network pharmacological analysis and experimental verification].

The present study aimed to explore the targets and mechanism of Mailuo Shutong Pills(MSP) in the treatment of ischemic stroke by network pharmacology, and verify the key targets through molecular docking and animal experiment, so as to provide a theoretical basis for the clinical application of MSP. The main chemical ingredients of MSP were obtained by searching against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and relevant literature. The potential targets of the ingredients of MSP in treating ischemic stroke were obtained from SwissTargetPrediction and DisGeNET. Protein-protein interaction(PPI) network was analyzed in STRING and plotted in Cytoscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out with DAVID. Molecular docking was simulated to determine the binding activity of active ingredients to key targets in AutoDock Vina. The mouse model of ischemic stroke was established. The mice were classified into a sham group, a model group, and an MSP group. After the administration, cerebral infarction volume was detected by 2,3,5-triphenyltetrazoliumchloride(TTC) staining, and Western blot was performed to determine the levels of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(AKT), nuclear factor-κB(NF-κB) and their phosphorylated proteins. A total of 222 ingredients of MSP were screened out, including beta-sitosterol, quercetin, licochalcone B, and lupiwighteone, which acted on 701 targets. Totally 1 079 targets associated with ischemic stroke were retrieved, among which 192 common targets were shared by MSP and ischemic stroke. The key targets included AKT1, phosphatidylinositol 3-kinase catalytic subunit alpha(PIK3 CA), phosphatidylinositol 3-kinase regulatory subunit 1(PIK3 R1), and nuclear factor-κB p65 subunit(RELA), which were mainly involved in PI3 K/AKT, tumor necrosis factor(TNF), and NF-κB signaling pathways. The results of molecular docking revealed that PI3 K, AKT1, and RELA had good binding ability to the active ingredients of MSP. The animal experiment results showed that compared with the model group, MSP decreased cerebral infarction volume, down-regulated the expression of p-NF-κB, and up-regulated the expression of p-PI3 K and p-AKT in mouse brain. In summary, the active ingredients in MSP may treat cerebral injury by activating PI3 K/AKT signaling pathway and inhibiting NF-κB signaling pathway.

Apigenin exerts chemopreventive effects on lung injury induced by SiO2 nanoparticles through the activation of Nrf2.

Apigenin (APG) is a flavonoid widely distributed in fruits, vegetables, and herbs, with comprehensive pharmacological effects. In this paper, we report that APG can elicit a protective effect, which is comparable to those induced by gymnoside II/n-BuOH extracts of Bletilla striata, on SiO2-induced lung injury in vitro and in vivo. In vitro experiments showed that APG (25 µM) could restore the SiO2-decreased A549 cell viability and lower the apoptotic rate and the production of intracellular reactive oxygen species (ROS) in A549 cells treated with nm SiO2. Western blot results showed that APG (25 µM) could increase the level of Nuclear factor E2-related factor 2 (Nrf2) and its downstream proteins. In vivo experiments showed that APG (20 mg/kg) could potently alleviate the SiO2-elicited lung injury by enhancing the Nrf2 expression and thereby suppressing Bax/Bcl-2 pathway. The present study suggests that APG can significantly alleviate the SiO2-induced lung injury both in vitro and in vivo through, at least partially, activating Nrf2 expression.

[Acupuncture and moxibustion treatment for dry eye disease: a network Meta-analysis of rando-mized controlled trial].

OBJECTIVE: A network Meta-analysis based on Bayesian theory was used to evaluate efficacy and safety of acupuncture and moxibustion in the treatment of dry eye disease(DED), so as to provide evidence-based research basis for clinical application. METHODS: Randomized controlled trials (RCT) for acupuncture and moxibustion treatment of DED published from the inception of database to November 25, 2020 were searched from PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang and VIP Database. Two reviewers independently screened the literatures, extracted the data. The quality of the included literature was evaluated, and network Meta-analysis was performed by using Stata14.0 and R4.0.3 software. RESULTS: A total of 71 literatures were identified, including 5 536 patients with DED, covering 11 different interventions. Network Meta-analysis showed that acupuncture+traditional Chinese medicine+artificial tears was the best treatment option in terms of the clinical effective rate, breakup time of tear film (BUT), Schirmer I test (SIT) with surface under cumulative ranking area value. Acupuncture+traditional Chinese medicine+artificial tears was better than artificial tears in the clinical effective rate (odds ratio［OR］=12.34, 95% confidence interval［CI］［4.72, 36.89］), BUT(mean differenc［MD］=2.76, 95%CI［0.16, 5.40］), SIT(MD=4.76, 95%CI［1.23, 8.29］). CONCLUSION: Acupuncture and moxibustion in the treatment of DED are generally better than artificial tears, and acupuncture-moxibustion combined with other traditional Chinese medicine therapy has the best effect.

Room Temperature Ferromagnetism of Monolayer Chromium Telluride with Perpendicular Magnetic Anisotropy.

The realization of long-range magnetic ordering in 2D systems can potentially revolutionize next-generation information technology. Here, the successful fabrication of crystalline Cr3 Te4 monolayers with room temperature (RT) ferromagnetism is reported. Using molecular beam epitaxy, the growth of 2D Cr3 Te4 films with monolayer thickness is demonstrated at low substrate temperatures (≈100 °C), compatible with Si complementary metal oxide semiconductor technology. X-ray magnetic circular dichroism measurements reveal a Curie temperature (Tc ) of v344 K for the Cr3 Te4 monolayer with an out-of-plane magnetic easy axis, which decreases to v240 K for the thicker film (≈7 nm) with an in-plane easy axis. The enhancement of ferromagnetic coupling and the magnetic anisotropy transition is ascribed to interfacial effects, in particular the orbital overlap at the monolayer Cr3 Te4 /graphite interface, supported by density-functional theory calculations. This work sheds light on the low-temperature scalable growth of 2D nonlayered materials with RT ferromagnetism for new magnetic and spintronic devices.