Network pharmacology strategy to investigate the pharmacological effects of Suanzaoren Decoction on insomnia

Abstract Suanzaoren Decoction (SZRD) is an ancient prescription used in the treatment of insomnia. This study aimed to investigate the components and targets of SZRD in treating insomnia. First, the compounds of five herbs in SZRD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the putative targets for treating insomnia were obtained from DrugBank to construct the herb-compound-target- disease network. A protein-protein interaction (PPI) network was constructed in the STRING database, and then Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the mechanism of action of intersection target. Finally, 30 mice were divided into five groups: control, model, and quercetin groups (100, 50, 25 mg/kg). The sleep latency and duration of pentobarbital-induced sleeping were measured. The production of interleukin-6 (IL-6) and γ-aminobutyric acid (γ-GABA) was detected by using an enzyme-linked immunosorbent assay kit (ELISA), and Gamma-aminobutyric acid type a receptor subunit alpha1 (GABRA1) was tested by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). A total of 152 active ingredients, including 80 putative targets of SZRD, were obtained. The main active compounds included quercetin and kaempferol, and the key targets involved IL-6 and nitric oxide synthase 3 (NOS3). The results of pathway enrichment analysis indicated that the putative targets of SZRD mainly participated in Neuroactive ligand-receptor interaction. The experiment of P-chlorophenylalanine (PCPA)-induced insomnia model showed that quercetin obviously shortened the sleep latency and prolonged the sleep duration of the insomnia model. The production of IL-6, γ-GABA, and GABRA1 mRNA was significantly increased in mice treated with quercetin. This study predicted the active ingredients and potential targets of SZRD on insomnia on the basis of a systematic network pharmacology approach and illustrated that SZRD might exert hypnotic effects via regulating IL-6, γ-GABA, and GABRA1

Preclinical study of suicide gene as a safety switch to control CAR-T cell cytotoxicity / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate whether AP1903, a small-molecule chemical inducer, can terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vivo and in vitro. Methods: CD19CAR-T cells over-expressing iCasp9 (iCasp9-CD19CAR-T) were constructed and co-incubated with AP1903. Then, the cell phenotype and apoptosis were detected by Flow cytometry, and the iCasp9/CID suicide gene system was verified on K562 and T cells, respectively. The cytotoxicity of iCasp9-CD19CAR-T cells was detected in vivo (survival rate of NCG mice bearing Raji cell transplanted xenograft) and in vitro (cell killing function was detected by Flow cytometry) under the administration of AP1903. Results: Compared with CD19CAR-T cells, iCasp9-CD19CAR-T cells showed in significant difference in proliferation, phenotype and cytotoxicity both in vitro and in vivo (all P>0.05). At 2 h after AP1903 administration, the apoptosis rates of K562 and T cells co-expressing iCasp9 and CD19CAR were (33.8±0.9)% and (27.95±0.35)%, respectively; and at 24 h after AP1903 administration, the apoptosis rates reached 100% in both cell lines. The in vitro cytotoxicity of iCasp9-CD19CAR-T cells induced by AP1903 was significantly lower than that without AP1903 treatment (P<0.01); the 60-day survival rate of mice bearing Raji cell transplanted tumor treated with AP1903-induced iCasp9-CD19CAR-T cells was also significantly lower than those treated with iCasp9-CD19CAR-T cells alone (P<0.01). Conclusion: AP1903 can effectively terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vitro and in vivo.

Efficacy and safety of umbilical cord mesenchymal stem cells for the treatment of patients with COVID-19

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

Detection rate of colonic polyp among patients who had undergone colonoscopy at gastroenterology unit of Serdang Hospital, Malaysia

@#The aim of this study was to evaluate the demography, and to determine the detection rate of polyps, and detection rate of adenoma at a Malaysian tertiary hospital.

Rare Occurrence of Type lll Membranoproliferative Glomerulonephritis in a patient with Hepatitis C in Sustained Virologic Response Phase

@#Hepatitis C virus (HCV) infection is known to cause acute and chronic active hepatitis. In addition, HCV also has systemic disorder involvement that links to various extra-hepatic complications. We report a case of a patient which has been diagnosed to have Hepatitis C Genotype 3A who has been started on antiviral. He achieved end treatment response and sustained virologic response. During routine follow up, he experienced acute kidney injury. Renal biopsy showed type III membranoproliferative glomerulonephritis. His proteinuria improved greatly with the addition of angiotensin converting enzyme inhibitor. This case highlights the possibility of appearance of HCV related glomerulonephritis in patient who has sustained virological response.

Antibacterial activity of the nisin-containing single-bond universal adhesive / 口腔疾病防治

Objective@#To investigate the antibacterial activity to Streptococcus mutans of a nisin-containing single-bond universal adhesive.@*Methods@#Nisin was mixed into the bonding agent to produce concentrations ranging from 0.01 g/mL to 0.05 g/mL for the experiments, and adhesive without nisin was used as the control. Dentin-resin specimens were prepared for the microtensile strength test to evaluate changes in the bonding strength. The proper concentrations were selected for more tests. ① An agar diffusion test was applied with filter paper to detect the release of nisin, and adhesive without nisin was used as the negative control, 0.01 g/mL Nisin aqueous solution was used as the positive control. ② Solidification; resin adhesive specimens were prepared for the assessment of direct contact inhibition activity. ③ Confocal laser scanning microscopy was used to examine the effect of the adhesive on the biological film activity and the ability of Streptococcus mutans to produce extracellular polysaccharides. @*Results @#Nisin did not significantly reduce the bond strength of the modified adhesive at 0.01-0.03 g/mL (P < 0.05); these concentrations were selected for the subsequent antibiosis experiment. Rings could not be observed in the agar diffusion test, except for in the group of adhesive modified with 0.01-0.03 g/mL nisin. Resin adhesive with 0.01-0.03 g/mL nisin could significantly inhibit the proliferation of Streptococcus mutans on the surface of the specimens. The confocal laser scanning microscopy results indicate that only the adhesive resin modified with nisin could reduce the bacteria in the biofilm and the production of extracellular polysaccharides.@*Conclusion@#Single-bond universal adhesive with 0.01-0.03 g/mL nisin can inhibit the growth of Streptococcus mutans and its biofilms on the bonding interface, as well as decrease the production of extracellular polysaccharides, and thus has the potential to decrease the occurrence of secondary caries.

Pulmonary Hemorrhage Associated With Severe Leptospirosis – The Role Of Low Dose Intravenous Methylprednisolone

@#Leptospirosis has a wide range of presentation which ranges from mild flu-like symptoms, to severe form including renal failure, liver failure, and hemorrhage. Pulmonary involvement can progress from subtle clinical features to life threatening pulmonary hemorrhage and acute respiratory distress syndrome. Although benefits of corticosteroids in adult respiratory distress syndrome have been proven and accepted, evidence for use of corticosteroids in pulmonary leptospirosis is still limited. Given the vasculitic nature of severe leptospirosis, it has been proposed that addition of intravenous corticosteroid therapy, particularly in cases of pulmonary involvement is beneficial. We report a case of leptospirosis with suspected pulmonary hemorrhage which deteriorates after a few days of admission in our tertiary hospital. We have demonstrated that the prescription of a lower dose of corticosteroid than what was widely reported in the literature can equally led to a satisfactory recovery of the pulmonary hemorrhage.

Influence of sahour meal on exercise performance and physiological responses in welltrained muslim runners during Ramadan

The objective of this study was to examine the influence of sahour meal on exercise performance, and physiological responses to a 10Km Time-Trial [10KTT] at two different times of the day during Ramadan. Three well-trained Muslim runners participated [age, 25 +/- 0.8years; maximal oxygen uptake, 54.87 +/- 3.45 ml.kg-1.min-1; body weight, 52.4 +/- 1.99 kg; height, 162.7 +/- 3.55 cm]. Subjects ran a 10KTT on four occasions: 8.00am [Am], and 5.00pm [Pm], separated by one day rest two weeks before Ramadan [BRam] and during the second week of Ramadan [DRam]. BRam, subjects consumed their usual diet. DRam, subjects consumed a standardized sahour meal containing 5.6 +/- 0.6kcal/kgBW; 2.3 +/- 0.1gCHO/kgBW; 0.6 +/- 0.0g Protein/kgBW; 0.5 +/- 0.0gFat/kgBW. During each 10KTT, the subject ran at 85%VO2max for the first two Km, and then at a self?selected speed then onwards. Blood samples were collected before the run, and at 2, and the end of 10 Km. Time to complete 10KTT were recorded. Urine specific gravity was measured before each run. There was no difference in hydration status for the Am and Pm runs BRam and DRam. Running performance DRamAM, was better compared to the DRamPm. There were also no changes in blood glucose BRam and DRam. Serum Testosterone was highest at the end of 10KTT DRamPm when compared to the DRamAm, and was generally higher than BRam. Serum Cortisol showed no differences between the trials. All runners did not experience dehydration, lack of energy nor drop in performance DRam. The results from this study suggest that when athletes are provided with a balanced sahour meal, during Ramadan, they can maintain their performance

Characterization of Calreticulin Expression in Mouse Endometrium during Embryo Implantation

Calreticulin (CRT), a Ca2+-binding storage protein and chaperone in the endoplasmic reticulum, modulates cell adhesiveness and integrin-dependent Ca2+ signaling. However, the role of CRT during implantation remains poorly understood. In the present study, we characterized the expression of CRT mRNA and the protein in mouse endometria from pregnancy DI to D7. Real-Time PCR and in situ hybridization results showed that the levels of CRT mRNA in the endometria of pregnant mice were significantly higher than those of non-pregnant mice (P<0.05), and increased gradually from pregnancy DI to D4, reaching the máximum level on D4, followed by a plateau from D4 to D7. Using immunofluorescence histochemistry and western blot, changes of CRT expression in the endometria of pregnant mice were consistent with the expression of CRT mRNA. Furthermore, antisense CRT oligodeoxynucleotide was injected into the uterus horns of pregnant mice (D3) to investígate its effect on embryo implantation. The result showed that the number of implanted embryos markedly decreased in the side of uterine horns receiving antisense CRT oligodeoxynucleotide(í><0.05). These findings suggest that CRT may play an important role in embryo implantation in mice.