Journal of Pharmaceutical and Biomedical Sciences

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https://imsear.searo.who.int/handle/123456789/149635

Editor : Dr Godfred Menezes,

ISSN: 2230-7885 (Online)

Frequency: 12 issues a year

Language:English

Web site: https://www.jpbms.info

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Diastolic Dysfunction in Patients with Metabolic Syndrome
(Lawarence Press Pvt. Ltd., 2020-01) Daphale, Ajay
Background The association of metabolic syndrome with the subclinical changes in the function and structure ofthe heart has been established clinically. Additionally, diastolic dysfunction and left ventricular hypertrophy werealso found to be closely associated with the metabolic syndrome. It has been identified in many of the previousstudies that LV dysfunction and LV hypertrophy are major risk factors of heart failure with preserved ejectionfraction.Aim The study was carried out to identify whether preclinical LV diastolic dysfunction can occur independent ofLV hypertrophy in MS or not.Methods 100 patients were taken for the study with 50 patients in the case group having MS and 50 patients inthe control group without MS. The patients who had any exiting cardiovascular disease including (heart failure,left ventricular ejection fraction [LVEF]<50%, coronary artery disease, or valvular heart disease were excluded fromthe study.Results The mean age of the case group was 45±8.5 years and that of the control group was 42±7.5 years therewas statistically significant difference among the various baseline characteristics between the case and controlgroups as the p value was found to be <0.05. All the ecocardioghraphic parameters had statistically significantdifference among the two groups except Left ventricular end diastolic dimension.Conclusion The study depicted a positive correlation between diastolic dysfunction and metabolic syndrome.Furthermore, it was observed in the study that metabolic syndrome proved to the baseline indicator of prognosisto diastolic dysfunction in the near future.
RNA-seq Analysis of Spinal Cord Tissues after Brachial Plexus Root Avulsion in Mice
(Lawarence Press Pvt. Ltd., 2020-06) Zhang, Yanjie; Duan, Juan; Qu, Yibo
Background Brachial plexus root avulsion (BPRA) can cause motor neuron death, nerve degeneration andupper limb motor dysfunction. The molecular mechanisms of motor neuron death and nerve degeneration arelargely unknown and there are no effective therapies to increase the functional recovery after BRPA.Aim: To detect the early pathway changes in spinal cord tissues after brachial plexus root avulsion.Methods A mouse brachial plexus avulsion and re-implantation model was constructed, and the C5-C7segments of the spinal cords were dissected three days after the surgery. We used RNA-seq to identify theexpression changes of genes and gene networks in spinal cord tissues.Results A total of 2253 differentially expressed genes were found significantly changed with 1852 upregulatedand 401 downregulated at 3 days after BPRA. Gene ontology (GO) enrichment analysis showed thatdifferentially expressed genes were most enriched in immune system process, regulation of immune systemprocess, defense response, plasma membrane part, extracellular region part, cell surface, protein binding,receptor binding, glycosaminoglycan binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathwayanalysis showed that the most enriched pathways included osteoclast differentiation, NF-kappa B, cytokinecytokine receptor interaction, TNF, hematopoietic cell lineage, complement and coagulation cascades, PI3KAkt, ECM-receptor interaction, NOD-like receptor, Toll-like receptor signaling pathway.Conclusions This study systematically identified the critical genes and signaling pathways in BPRA pathology.These results expand our understanding of the complex molecular mechanisms involved in BPRA and provide afoundation for future research of spinal cord tissue injury and repair.
Developing an UPLC-MSMS Method to Quantify a Novel Anticancer Chalcone BOC26P for Its Pharmacokinetic Study In vivo
(Lawarence Press Pvt. Ltd., 2019-08) Lin, Lina; Chen, Lexing; Xu, Jun; Cai, Shaohui; Lu, Danyi
Objective BOC26P is a potent anticancer candidate which inhibits microtubule polymerization and shows strongcytotoxic activity against numerous cancer cell lines and drug resistant cell lines. To support the pharmacokineticstudy of BOC26P, a rapid, selective and reproducible UPLC-MS/MS method was developed.Method Dexamethasone sodium phosphate (DSP) was used as an internal standard (IS). Following proteinprecipitation by using methanol-acetonitrile solution (1:1, v/v) with an internal standard DSP, the processedsamples were chromatographed on an UPLC X Bridge 71 TM C8 column (4.6 mm × 100 mm, 3.5 μm) with a mobilephase that consisted of acetonitrile and 2mmol/L ammonium acetate aqueous solution (containing 0.25%ammonia) with a gradient elution pumped at a flow rate of 0.4 mL/min. Mass spectrometric detection wasperformed in the positive electrospray ionization mode by multiple reaction monitoring (m/z 428.84→198.92 and472.90→434.93 for BOC26P and DSP, respectively). The quantification of BOC26P in rat plasma was fully verified.Results The linearity was established in the range of 50 to 2000 ng/mL(r2≥0.99). The recovery of BOC26P fromspiked plasma were ranged from 96.7% to 110.5%. This method showed acceptable accuracy (3.7% to 6.3%) andprecision (1.5% to 3.1%) both of intra- and inter-day.Conclusion The developed method was successfully applied for three intravenous dose (2, 5, 12.5 mg/kg BOC26P)pharmacokinetics in male and female rats
Behavioral, Biochemical and Pathological Characterization of a new MDX Mouse Model of Duchenne Muscular Dystrophy
(Lawarence Press Pvt. Ltd., 2020-06) Wang, Fengjiao; Wen, Jing; Guo, Baojian; Wu, Liangmiao; Liu, Zheng; Zaijun, Zhang
Background Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due tomutations in the dystrophin gene. Animal models that accurately reflect pathological conditions and diseasecharacteristics are key factors in the discovery and development of new anti-DMD drugs.Aim Here, we evaluated motor behavior, pathological and biochemical characters of a new DMD mouse modelbuilt up by the Nanjing Biomedical Research Institute of Nanjing University (NBRI).Methods The pole test and open-field test were used to assess the movement disorders in DMD mouse model.The gastrocnemius (GAS), biceps, triceps, soleus, and tibialis anterior muscles of mice were subjected to weight analysis to evaluate the skeletal muscle pseudohypertrophy. Meanwhile, immunofluorescence andWestern blotting were used to detect the expression of dystrophin in the GAS. Serum levels of creatine kinase(CK) and lactate dehydrogenase (LDH) that accurately reflect muscle damage were detected. Masson stainingwas used to evaluate the fibrosis of GAS and diaphragm (DIA).Results The novel DMD mouse showed significant behavioral disorders and exhibited high serum levels of CKand LDH. Western blotting and immunofluorescence staining showed decreased significantly with dystrophinlevel in the GAS. Besides, the mdx mouse of DMD developed fibrosis in both GAS and DIA.Conclusion Taken together, our results indicated that the behavioral, biochemical and pathologicalcharacterization of the mdx mouse model is similar to human DMD. This mdx mouse model may provideinsights into the pathophysiology of DMD and the effects of anti-DMD drugs.
Methyltransferase Like 3 and Fat Mass and Obesity-Associated Protein Are Required for H7N9 Infection in Cell Culture
(Lawarence Press Pvt. Ltd., 2020-06) Luo, Ying; Sun, Ying; Liu, Hui; Peng, Bo; Wu, Weihua; Wang, Xin; Zheng, Qing; Fang, Shisong
Background METTL3 (methyltransferase like 3) and FTO (fat mass and obesity-associated protein) are criticalfor establishing and regulating the m6A (N6-methyladenosine) modification, but very little is known about thefunction of m6A in the immune system or its role in interactions within the host immune system.Methods Western blotting experiment was used to check the expression of the host proteins related to m6Amodification after H7N9 influenza virus infection. Immunofluorescence experiment was used to identifywhether the subcellular localization of related proteins. Moreover, we knocked down and over expressendogenous METTL3 or FTO in A549 cells, and then infected the cells with H7N9 to test whethermethyltransferases or demethylases affect H7N9 replication.Result We confirmed that the expression pattern of m6A proteins was altered during H7N9 infection. METTL3and FTO were located in the nucleus, and YTHDF3 was located in the cytoplasm. Furthermore, our resultsdemonstrate that downregulation of METTL3 or FTO expression in A549 cells severely impairs viral proteinexpression and H7N9 infection.Conclusions METTL3 and FTO are critical for H7N9 replication which may represent a new mechanism for thecontrol of H7N9 replication and host-pathogen interactions.
Studies on the Anti-Proliferative Effects and Molecular Mechanism of a Novel Small Molecular BOC26P in Breast Cancer
(Lawarence Press Pvt. Ltd., 2020-06) Li, Xiaojuan; Li, Shiying; Li, Qiuwen; Lin, Lina; Cai, Shaohui; Xu, Jun
Background To explore the pharmacodynamic evaluation and mechanism research of BOC26P against breastcancer, and to provide a basis for the treatment of breast cancer.Method MTT assay was used to detect the cytotoxicity of BOC26P against 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231and MCF-7), and as well as the non-tumor cell lines MCF-10A, in variousdrug concentrations (from 0.004 to 1 μM). Western Blotting and Real-Time PCR assay were used to detect therelative protein and gene expression level after treatment with BOC26P in MCF-7/TAX. The effect of BOC26Pon Specific fluorescent P-gp substrate accumulation in MCF-7/TAX was analyzed by flow cytometry; Moleculardocking was used to analyze the binding capacity between BOC26P, Cyclosporine A, and Verapamil. FCM assaystaining with Annexin V-FITC/PI and Propidium iodide was used to measure the apoptosis and the cell cycleafter treatment with BOC26P in MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7; Detection ofmitochondrial membrane potential after treatment with BOC26P inMCF-7/TAX, MDA-MB-231/PT, MDA-MB231and MCF-7; Western Blotting and Real-Time PCR assay was used to detect the apoptosis relative proteinand gene expression level after treatment with BOC26P in MDA-MB-231, MCF-7, MDA-MB-231/PT, and MCF7/ADR.Results Cytotoxicity assay showed that BOC26P could effectively suppress 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7) with an IC50 value of under 0.5 μM. The IC50 value ofBOC26P on non-tumor cells MCF-10A was 32.29 μM. The binding ability of BOC26P to P-gp in breast cancercells was weak. There was no significant effect on the intracellular accumulation of Rhodamin 123(Rh123), Pgp binding specific fluorescence substrate, and multi-drug resistance protein P-gp expression in MCF-7/ADRand MDA-MB-231/PT tumor cells; BOC26P induced MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231 and MCF-7cells cycle arrest at G2/M phase and lead to cell apoptosis. BOC26P induced significant activation of p53protein in MCF-7/ADR and MAD-MB-231/TAX cells. Under the same conditions, BOC26P promoted Baxexpression while inhibited Bcl-2 expression, and could significantly cause activation of Cleveland PARP andClevead Caspase3. The results demonstrated that BOC26P may induce apoptosis through the death receptorapoptosis pathway.Conclusion It is known that BOC26P has a significant proliferation inhibitory effect on breast cancer cellswithout serious side effects. BOC26P has the Potential to be developed into a clinical substitute drug for triple-
Comparing Thyroid Abnormalities with Severity of Chronic Renal Failure
(Lawarence Press Pvt. Ltd., 2020-01) Dakre, Abhijit; Idhol, Sagar
Background Thyroid dysfunction affects renal physiology and development, whereas kidney disease could resultin thyroid dysfunction. Disorders of the thyroid and kidney may co-exist with common etiological factors. In addition,treatment strategies of one disease may affect those of other organ. Decrease in iodothyronines is associated withreduced blood flow to kidneys and decreased glomerular filtration rate(GFR) along with alteration in tubularreabsorption resulting in decrease in water excretion. Aim To estimate thyroid hormone levels i.e. T3, T4 & TSH inCRF. Methods An observational study was carried out at the Dr. Panjabrao Deshmukh Memorial MedicalCollege, Amravati, Maharashtra in and out patients of the dialysis unit. The study was carried out for a period from12th of August, 2019 to 12th of December 2019. The patients were divided into two groups namely case and controlwith 35 male patients each. In the case group patients having serum creatinine >5.5md/dl and urea >55 mg/dl withsymptoms of chronic renal failure were included. However, in the control group 35 healthy male patients wereincluded in the study. Results It was identified that Serum creatinine and T3 and Serum creatinine and T4 showednegative correlation. This implies that if the serum creatinine level rises T3 and T4 levels will fall and vice versa.In the case group majority of the patients had normal thyroid function while 14.28% had hypothyroidism.Hypothyroidism was present in 5 of the patients with serum creatinine >6.0 mg/dl. Conclusion In the light of theresults it was identified that the mean T3 and T4 levels decreased while TSH levels increased significantly in thecase group as compared to the control group. Furthermore, it was identified in the study that the levels of T3, T4decreased and TSH increased as severity renal failure increased.
Polymorphism of Vitamin D Receptor Gene -Taq1 (RS 731236) Associated With Plasma Vitamin D Group Levels Among Breast Cancer Patients in H. Adam Malik Hospital, Medan
(Lawarence Press Pvt. Ltd., 2020-02) Waraztuty, Ika; Siregar, Yahwardiah; Siregar, Kamal Basri; Wanandi, Septelia Inawati; Betty, Betty
Aim Breast cancer was one of the most cancer occurred in women worldwide. Taq 1 polymorphism, a silent SNP,was thought to be genetic risk factor for breast cancer. This study was aimed to understand the relationshipbetween vitamin D receptor gene–Taq 1 (RS 731236) polymorphism and plasma vitamin D level among breastcancer patients in RSU H. Adam Malik Medan. Material and Methods Blood sample was collected from 53 newbreast cancer cases that had not received any chemotherapy. DNA isolation and gene amplification was doneusing PCR then followed with RFLP using Taq 1 restriction enzyme. The level of 25(OH)D was measured usingELISA. Result and Discussion Study results showed TT genotype was 92.5%, TC genotype was 7.5%, CC genotypewas 0 % using Hardy-Winberg Equilibrium (HWE) p=0.77, mean value of vitamin D level in study subject was28.16 ng/ml (CI 95%: 25.71-30.60). Fisher exact test analysis concluded that polymorphism of vitamin D receptorgene-Taq1 associated with plasma vitamin D group levels among breast cancer patients in H. Adam MalikHospital, Medan (p= 0.033) but there was no difference in mean plasma vitamin D levels between genotypegroups of Taq1 (p=0.141). Conclusion Vitamin D receptor gene-Taq1 polymorphism was associated with plasmavitamin D group level and but no significant differences in mean plasma vitamin D levels between genotypegroups of Taq1.
Study On the Validity Of Instant Photography Method For Dietary Assessment In Undergraduate College Students
(Lawarence Press Pvt. Ltd., 2019-07) Ding, Chenghe; Li, Sha; Ayinla, Osseni Issideen; Chen, Junliang; Chen, Xingyi; Lai, Zhiwei; Pu, Liuzhen; Huang, Qiangwei; Chen, Xiaolin; Cheng, Zijian; Lijun, Wang; Huang, Qiaoting
Background A healthy diet in a college student life is critical to ensure their normal growth, study anddevelopment.Aim In order to accurately assess the dietary pattern of college students and guide it, our study aims to evaluatethe validity of instant photography as an alternative dietary assessment method in college students.Methods Nine participants were enrolled and given a presentation on dietary assessment methods, includingweighing, 24-hour recall, and instant photography. The participants took pictures of their foods from three anglesbefore and after eating for constant seven days, foods weighing was completed by others. Then, the participantsrecalled the foods’ weights after 24 hours. Two trained observers estimated food weight from the digital images(n = 285) gathered at the end of the study with the aid of Chinese food atlas reference.Results Instant photograph showed significant correlation with weighing method on food weights of grains,tubers, vegetables, fruits, meat and eggs (all P ≤ 0.01). 24-hour method had similar correlation with weighingmethod on food weights except fruits. Compared with 24-hour recall, instant photograph displayedunderestimation on weights of grains, tubers, vegetables, and meat. However, instant photograph had moreaccurate estimations on weights of fruits and egg. Furthermore, compared with nutrients data from weighingmethod, both instant photography and 24-hour recall methods showed promising estimations on the amounts ofenergy, protein, fat, carbohydrate, vitamin A, vitamin C, vitamin E, calcium, iron and zinc (all P < 0.001). Comparedwith 24-hour recall, instant photograph displayed underestimation on the amounts of energy, protein, fat,carbohydrate, vitamin A, vitamin C, vitamin E, zinc. However, instant photograph had a more accurate estimationon calcium.
Tissue Distribution Study On Apocynin Nitrone Derivative AN-1 After Intravenous Administration
(Lawarence Press Pvt. Ltd., 2019-06) Li, Huirou; Liang, Zhiyan; Wang, Kaiyu; Ouyang, Jiabi; al., Mohui Yang et
Background Apocynin, a main component extracted from the root of Picrorhiza kurroa Royle, was a well-knownNADPH oxidase inhibitor and reported to have effect on lung injury, liver injury, diabetes and asthma. AN-1, anitrone derivative of apocynin, was found to exhibit significant effect on treatment of acute lung injury.Aim In order to carry out further preclinical study, it is important to reveal in vivo disposition of AN-1. A simple andrapid high-performance liquid chromatography (HPLC) method was developed to disclose the tissue distributionbehavior of AN-1 in Sprague-Dawley (SD) rats.Methods A HPLC method was developed and validated to measure the concentration of AN-1 in tissue sampleswith carbamazepine as internal standard (IS). The mobile phase consisted of water and methanol (47:53, v/v), theflow rate was 1 mL/min, and an ultraviolet (UV) detector was used at wavelength of 279 nm. The tissue distributionstudy of AN-1 was performed in Sprague-Dawley (SD) rats after a single intravenous dose of 40 mg/kg.Results The developed HPLC-UV method was of good specificity, precision (< 4%), accuracy (90-97%) and recovery(88-104%) for analysis of AN-1 in tissue samples of rats. The linear range was established over a concentrationrange 0.2-50 µg/mL (r2 > 0.998) in tissues including heart, liver, spleen, lung, kidney and brain. After administration,AN-1 was rapidly distributed in tissues and reached peak concentration with time, which showed a high distribution
Prognostic Risk Model of Colorectal Cancer Constructed by Bioinformatics Method and Functional Study of The Gene CLCA1 & SPINK4
(Lawarence Press Pvt. Ltd., 2020-06) Li, Shiying; Liu, Haowei; Zhao, Yongming; Zeng, Yingxing; Xu, Jun
Background Colorectal cancer (CRC) is the most common malignant tumor of digestive system. The metastasesis the main cause of mortality in CRC patients, of whom the initial diagnosis is about 25%. In our study, weaimed to identify potential gene biomarkers based on RNA sequencing data to predict and improve CRCpatient survival.Method In this study, by screening differentially expressed genes of colon cancer related to liver metastasis, asurvival prognostic risk model was constructed by bioinformatics analysis. Here, we conducted our data mininganalysis for CRC by integrating the differentially expressed genes acquired from Gene Expression Omnibus(GEO) database by primary tumor versus liver metastasis (GSE81582，GSE41258，GSE49355，GSE68468)into The Cancer Genome Atlas (TCGA) database which includes 415 primary tumor and 132 liver metastasistissue. At the same time, we used transwell, RT-PCR and western to examine the effects of CLCA1 and SPINK4on the migration of colorectal cancer cells at the cell level.Results We identified intersections of 197 genes (117 up-regulated and 80 down-regulated) between GEO dataand TCGA data. Differentially expressed genes in TCGA-COAD by single factor cox analysis, lasso cycle trainingand multifactor cox analysis composed a survival prognosis prediction model consisted of 7 genes ORM1,CLCA1, C8B, SPINK4, ALDOB, GAMT, C8G. And results of transwell experiments showed that high expression ofCLCA1 and SPINK4 can inhibit the migration ability of colon cancer cells LOVO and SW620, meanwhile westernblotting showed that the high expression of both genes can upregulate the expression of epithelial phenotypicmarker E-cadherin, and Vimentin expression is down-regulated.Conclusion In this study, 197 differentially expressed genes were selected and a relatively robust survivalprognosis prediction model was constructed. The model consisted of seven genes: GAMT, C8G, ORM1, CLCA1,C8B, SPINK4, and ALDOB. At the same time, we found that CLCA1 and SPINK4 are closely related to survivalprognosis. The predictive model nomogram will enable patients with CRC to be more accurately managed intrials testing new drugs and in clinical practice.
Development of a LC-MS/MS Method for a New Ortho-aryl Chalcone Compound of OC26 and its Application to Bile
(Lawarence Press Pvt. Ltd., 2020-02) Chen, Lexing; Liu, Jiang; Gan, Xia; Jiang, Zhounan; Xu, Jun; Cai, Shaohui
Background OC26 and its pro-drug BOC26P, both ortho-aryl chalcone compounds, showed a well-definedantitumor activity in various cancer cells especially in drug-resistant tumor cell lines.Aim The purpose of this study was to investigate the bile excretion characteristics of OC26 after OC26 and BOC26Padministered in rats respectively.Method An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method wasdeveloped and validated for OC26 in rat bile. Liquid-liquid extraction with ethyl acetate method was use to pretreatthe bile samples. After that, a gradient mobile phase at a flow rate 0.5mL/min of acetonitrile and 2mM CH3COONH4with 0.1% aqueous ammonia solution (v/v) and the positive ion alternate mode separated and quantified OC26.Bile samples were collected from rats after intravenous injection (i.v) 12.5mg/kg of OC26 and BOC26P, respectively.Results For method validation, the method showed high extraction recovery. The assay showed a good linearitywith correlation coefficient >0.99 at the concentration ranges of 20-2000ng/mL. All data were within the requiredlimits. The bile excretion results showed that the excretion amount of OC26 was gradually stabilized after 2h. Theaccumulative excretion percentage of OC26 after i.v 12.5mg/kg BOC26P was significantly higher than that of OC26after i.v 12.5mg/kg OC26. Significant gender differences were also observed in bile excretion of OC26.Conclusion This method was selective, sensitive and reliable and successfully applied to the bile excretion of OC26.This study provided theoretical basis for OC26 further research.
Cross-Allergy of Sulfonamide-Containing Drugs in Sulfonamide Allergic Patients: A Literature Review and Case Study
(Lawarence Press Pvt. Ltd., 2020-03) Feng, Weile; Huang, Jiawen; Tang, Yuwen; Zhang, Zhidong; Feng, Xiaofei; Zhang, Jianping
The purpose of this study is to find out whether there are broad cross-reactivity between antibacterial and nonantibacterial sulfonamide agents, the method of the study contained two parts, one is literature research mainlyfrom PubMed database by using the MeSH terms (“Drug name” + allergy); (“Drug name” + hypersensitivity);(“Drug name” + cross-allergenicity) and (“Drug name + cross-reactivity), the search drugs included somecommonly seen medication such as carbonic anhydrase inhibitor, COX-2 inhibitor, loop diuretic, sulfonylurea,thiazide and certain antiviral drugs; the other parts of this thesis is to conduct a statistical review, we screen outpatients who have a previous allergic history of antimicrobial sulfonamides from hospital medical record systemduring Jan 1st, 2015 to Dec 31th, 2016, we did a descriptive statistics of general patients medical information,analyze the suspect cases which patients present potential allergic reaction after using non-antimicrobialsulfonamides agents. Result of literature research reveal there are no convincing evidences and research toconfirm there are bored allergenicity between non-antimicrobial sulfonamides and antimicrobial sulfonamide inthe aspects of chemical structure, immunological study, and large scale population study as well; Result ofhospital patient’s statistics found out there are only 3 suspected cases that the patients were having adverseeffect during their pharmacotherapy from 506 cases. However, we did not found any strong correlation of broadallergenicity between non-antimicrobial sulfonamides and antimicrobial sulfonamides from these suspectedcases. Conclusion: There is minimal evidence of cross-reactivity between the antimicrobial sulfonamides and thenon-antimicrobial sulfonamides. However, the non-antimicrobial sulfonamides are rarely implicated inhypersensitivity reactions as well, so it is impossible to say with certainty that cross-reactivity does not occur.
Drug Release and Pharmacokinetics Behavior of a Simple Ethylcellulose Coating Pulsatile Tablet of Time-controlled Explosive System
(Lawarence Press Pvt. Ltd., 2020-03) Yang, Mohui; Xingli Wang; Jiabi Ouyang; Zhen Zhang; Tan, Yani; Li, Sha
Background The time rhythm of human body is associated with the occurrence and development of manydiseases. Kinds of diseases of particular onset biorhythm provided the room for the development ofchronopharmacological drug delivery systems.Aim In this work, the drug release and pharmacokinetics behavior of metoprolol tartrate (MT) pulsatile tabletdeveloped in our lab was investigated to figure out its feasibility of convenient drug taking to exert effectivechronotherapy for cardiovascular diseases like hypertension and angina pectoris.Methods The in vitro release behavior of MT pulsatile tablets was investigated by using basket method. Theappearance and morphology of MT pulsatile tablets during drug release was observed by naked eye and scanning electronic microscope, respectively. In vivo pharmacokinetics performance was studied in NewZealand rabbits.Results The lag time of MT pulsatile tablets was approximately 7 h in vitro, and a fast release was observedthereafter, with more than 90% releasing within 10 min. The pharmacokinetics study in rabbits demonstrateda perfect consistence in the absorption lag time of 7.04 ± 0.29 h in vivo. Compared with the marketedconventional tablet, the MT pulsatile tablet showed a bioequivalence in absorption extent with a relativebioavailability of 110.04%, but not in absorption rate.Conclusion The designed lag time of 7 hours enabled the MT pulsatile tablets to achieve effectivechronotherapy for cardiovascular diseases like hypertension and angina pectoris with a high attack rhythmaround 4:00-6:00 A.M by giving medicine conveniently around 22:00 P.M. the night before.
Celsr3 is required in mouse hippocampal intrinsic wiring and spatial learning
(Lawarence Press Pvt. Ltd., 2020-05) Fu, Hongbiao; Duan, Juan
Background The atypical cadherin Celsr3, which belongs to the core planar cell polarity group, orchestratesaxonal guidance and network wiring. Previous work using regional inactivation of Celsr3 in forebrain showedthat Celsr3 is widely involved in hippocampal maturation and connectivity. However, inactivation in the wholeforebrain does not provide sufficient specificity to address the function of Celsr3 in detail.Method We studied the Celsr3|Emx1 mouse mutant model, in which Celsr3 is selectively inactivated inhippocampal projection neurons, but not in entorhinal cortex, basal ganglia and interneurons.Result In that mutant, the hippocampal cytoarchitecture was almost normal. Inactivation of Celsr3 inprojection neurons perturbed intrinsic hippocampal wiring. Consistent with wiring defects, Celsr3|Emx1mutant mice showed impaired learning and memory, and were less anxiety-prone than control mice.Conclusion Celsr3|Emx1 mutant mice provide a simple way to study the consequences of defectivehippocampal wiring in absence of drastic structural anomalies.
Sceletium Tortuosum: Effects on Central Nervous System and Related Disease
(Lawarence Press Pvt. Ltd., 2020-06) Luo, Yangwen; Wen, Jing; Kanfer, Isadore; Yu, Pei; Patnala, Srinivas
Sceletium tortuosum is a well-known medicinal plant in South Africa with potential applications. Its rawmaterial, extracts and isolated alkaloids are used as dietary supplements, natural medicines and health food.In this paper, methods of planting, extraction, isolation and identification of Sceletium tortuosum, as well as itschemical structure of main extracted alkaloids, their related pharmacological effects and mechanisms fortreating the disease are reviewed. In general, Sceletium tortuosum is active to central nervous system (CNS) byinhibiting phosphodiesterase isozyme 4 (PDE4), serotonin (5-HT) uptake and acetylcholinesterase (AChE). Italso acts as a monoamine releasing agent for antidepressant effects. Therefore, it is a useful therapeutic agentin clinical use.
A Polypeptide Specifically Binds to RAGE can Alleviate the Destroy of Blood Brain-Barrier caused by Amyloid beta
(Lawarence Press Pvt. Ltd., 2020-04) Huang, Yi-yun; Zhu, Yu-jie; Wang, Shan; Zheng, Qing
Background The interaction of the receptor for advanced glycation end product (RAGE) on blood-brain-barrier(BBB) with amyloid β (Aβ) plays an important role in the occurrence and development of AD. RP1 is a RAGEspecific binding peptide, which was discovered in our previous experiments, and it has been proved to beeffective on AD cell model, however, its effects on BBB tight junctions (TJs) and on Aβ transport into the brain isunclear.Methods Immunofluorescence experiment was used to identify whether RP1 bound with RAGE specifically.BEnd3-immortalized mouse brain microvascular endothelial cells were used to construct a BBB model. TEER andFD40 tests were used to confirm the stability of the BBB model, and the colocalization of the RP1 and RAGE onthe surface bEnd3 cells was observed with confocal microscopy.Results We confirmed that RP1 can bind to RAGE specifically in vitro. Functional analyses indicated that RP1 caneffectively alleviate the destroy of TJs of BBB and the decrease of permeability of BBB caused by Aβ. Furthermore,RP1 can competitively inhibit the interaction of Aβ with the RAGE in vitro, and effectively inhibit Aβ transport intothe brain.Conclusion RP1 can inhibit BBB damage induced by Aβ and block RAGE-Aβ interaction effectively, and RP1 canbe a candidate of RAGE inhibitors contributing to AD treatment
Clinical study of Perioperative Use of Levosimendan in Patients Undergoing Heart Valve Replacement
(Lawarence Press Pvt. Ltd., 2020-04) Huang, Jiawen; Huang, Chengfeng; Lin, Zhaoming; Zhang, Zhidong
Objective To investigate the clinical effect of levosimendan in perioperative aortic and/or mitral valvereplacement. Methods Patients undergoing open heart aortic and/or mitral valve replacement in our hospitalfrom January 2018 to December 2019 were enrolled. 45 patients in the control group received routineperioperative treatment based on dopamine, while 45 patients in the research group received continuousperioperative administration of levosimendan injection for 24h on the basis of routine treatment. The leftventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd) and left ventricular end-systolicdiameter (LVDs) were evaluated by color doppler echocardiography before and one week after surgery.Postoperative mechanical ventilation weaning time, length of ICU stays, number of vasoactive drugs used andwithdrawal time; indexes of liver and kidney function before and on the day after surgery to 10 days after surgery;use of in vitro support techniques such as aortic balloon pulsation (IABP), continuous renal replacement therapy(CRRT) and extracorporeal membrane oxygenation (ECMO) within 5 days of perioperative period. Results Theimprovement of LVDs and LVEF in the study group using levosimendan one week after the operation wassignificantly better than that in the control group (P value was 0.013 and 0.001, respectively), and fewer kinds ofvasoactive drugs were needed (P<0.001), and the risk of postoperative AKI in the study group was significantlylower than that in the control group (P=0.047). Conclusion The perioperative use of levosimendan can effectivelypromote the recovery of cardiac systolic function and reduce the risk of postoperative AKI.
Minor Sesquiterpenoid and Steroid Constitutes from Azadirachta indica A. Juss and Their Cytotoxic Activity
(Lawarence Press Pvt. Ltd., 2019-05) Dong, Hua; Xiaofeng Lu; Zi, Jiachen; Fan, Xiaona
Background Neem (Azadirachta indica A. Juss) is a plant belonging to the meliaceae family. It was used widely asherbal medicine in ancient India and Burma. It possesses a variety of chemical constitutes. Recent studies showedthat some of major constitutes have remarkable anticancer activities. However, the minor constitutes in neem arestill studied insufficiently.Aim The aim of the study is to identify the minor constitutes in neem, and investigate their cytotoxic activity.Material & methods The dry seeds of neem were extracted with 95% ethanol. The ethyl acetate fraction of theextract was systematically separated by silica gel, Sephadex LH-20, High Performance Liquid Chromatography(HPLC) and other chromatographic techniques. The structures of the resulting isolates were elucidated byspectroscopic methods, such as mass spectrum (MS), nuclear magnetic resonance spectrum (NMR), etc.Results A sesquiterpenoid, 11,13-dihydroqinghaosu V (1), together with two known steroids, (24R)-ergosta5,7,22E-trien-3β-ol (2) and 5α,8α-epidioxiergosta-6,22-dien-3β-ol (3), was isolated from the dry seeds of neem. 1is a compound which is isolated from nature for the first time. In vitro cytotoxic bioassays showed that compound1 selectively inhibited the growth of Hela cell lines, with an IC50 value of 37.26 ±6.02 µM.Conclusion The study indicated that besides some major constituents of neem possessing anticancer activity, itsminor metabolites may also inhibit growth of cancer cells
Microwave Reaction Improved Heterocyclization of Quinazolinone Ring in Synthesis of Erlotinib Analogues
(Lawarence Press Pvt. Ltd., 2020-05) Man, Jianghong; Qi, Jianbin; Jiang, Jie; Li, Sha
Background Tinibs were a kind of important epidermal growth factor receptor (EGFR) inhibitors used aspotential therapeutic agents in treating non-small cell lung cancer (NSCLC) in clinic. The drug resistance ofclinical used tinibs made the development of more active tinib analogues an attractive field in research.Quinazoline ring was regarded as the key fragment in tinibs and quinazolinone was indispensible intermediatein the synthesis of quinazoline. Thus, synthesis of quinazolinone intermediates was a key step which wouldfurther limit the overall yield of final product of tinib analogues. However, the commonly used synthetic scheme was somewhat complicated and time consuming with relatively low yield in heterocylization ofquinazolinone and its derivatives.Aim In this work, we intended to explore an effective way to improve synthesis of heterocyclization of 6,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one (compound 5), the key fragment of erlotinib analogues, in bothreaction procedure and yield, thus to provide reference to synthesis of other quinazolinone derivatives.Methods A simple microwave-assisted one-pot reaction was employed to improve the synthesis ofheterocyclization of quinazolinone ring. The reaction conditions, including microwave power, temperature andtime of reaction, were screened to achieve high yield under simple operation.Results 6,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one (compound 5) was successfully synthesized fromstarting material of 4,5-bis(2-methoxyethoxy)-2-nitrobenzonitrile by microwave reaction, which was finished in1 hour just by one step. The yield of heterocyclization was increased from 29.8% of commonly used three-stepscheme to 50% herein.Conclusion Microwave reaction efficiently improved synthesis of heterocyclization of 6,7-bis(2-methoxyethoxy)quinazolin-4(3H)-one into "quinazolinone in both synthetic procedure and yield. The resultsmay provide valuable reference to synthesis of other quinazolinone derivatives.

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