scholarly journals Catalpol in Diabetes and its Complications: A Review of Pharmacology, Pharmacokinetics, and Safety

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3302 ◽  
Author(s):  
Ying Bai ◽  
Ruyuan Zhu ◽  
Yimiao Tian ◽  
Rui Li ◽  
Beibei Chen ◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Pharmacokinetic Profile ◽  
Underlying Mechanism ◽  
Oral Dosage ◽  
Drug Candidate ◽  
General View ◽  
Knowledge Infrastructure ◽  
Novel Scaffold ◽  
Chinese National Knowledge Infrastructure ◽  
Shed Light

This review aimed to provide a general view of catalpol in protection against diabetes and diabetic complications, as well as its pharmacokinetics and safety concerns. The following databases were consulted with the retrieval of more than 100 publications through June 2019: PubMed, Chinese National Knowledge Infrastructure, WanFang Data, and web of science. Catalpol exerts an anti-diabetic effect in different animal models with an oral dosage ranging from 2.5 to 200 mg/kg in rats and 10 to 200 mg/kg in mice. Besides, catalpol may prevent the development of diabetic complications in kidney, heart, central nervous system, and bone. The underlying mechanism may be associated with an inhibition of inflammation, oxidative stress, and apoptosis through modulation of various cellular signaling, such as AMPK/PI3K/Akt, PPAR/ACC, JNK/NF-κB, and AGE/RAGE/NOX4 signaling pathways, as well as PKCγ and Cav-1 expression. The pharmacokinetic profile reveals that catalpol could pass the blood-brain barrier and has a potential to be orally administrated. Taken together, catalpol is a well-tolerated natural compound with promising pharmacological actions in protection against diabetes and diabetic complications via multi-targets, offering a novel scaffold for the development of anti-diabetic drug candidate. Further prospective and well-designed clinical trials will shed light on the potential of clinical usage of catalpol.

scholarly journals Pharmacokinetic Study and Optimal Formulation of New Anti-Parkinson Natural Compound Schisantherin A

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Fei Sa ◽  
Bao Jian Guo ◽  
Sai Li ◽  
Zai Jun Zhang ◽  
Hok Man Chan ◽  
...  
Keyword(s):  
Pharmacokinetic Profile ◽  
Absolute Bioavailability ◽  
Drug Candidate ◽  
Vacuum Degasser ◽  
Ultraviolet Detector ◽  
Novel Approach ◽  
Cns Drugs ◽  
Oral Therapeutic ◽  
Shed Light ◽  
Schisantherin A

Our recent studies showed that schisantherin A (StA) is a promising candidate for PD treatment, but the pharmacokinetic profile of StA is largely unknown. The effects of different formulations on the pharmacokinetics and bioavailability of StA were investigated by HPLC equipped with a vacuum degasser, a quaternary pump, a manual sampler, and an ultraviolet detector. The absolute bioavailability of StA in nanoemulsion formulation was significantly increased from 4.3% to 47.3%. To the best of our knowledge, this is the first report of absolute bioavailability for StA in rats and successful increase of bioavailability of StA by nanoemulsion formulation. The pharmacokinetic profiles of StA could be significantly improved by a safe nanoemulsion formulation. This study provides a successful example of advanced delivery system for improving the bioavailability of potential central nervous system (CNS) drug candidate with poor solubility. This novel approach could be an effective alternative solution to overcome the shortcomings of conventional poor drug delivery of CNS drugs. The results of present study not only indicate that StA has potential to be developed as a promising oral therapeutic agent for the management of PD but also shed light on novel way to improve bioavailability of PD drugs.

FIXED-DOSE COMBINATION DRUGS AS TABLET IN TABLET: A REVIEW

2021 ◽  
Vol 1 (9) ◽  
pp. 169-177
Author(s):  
Pavazhaviji P ◽  
Rajalakshmi A. N
Keyword(s):  
Drug Release ◽  
Patient Compliance ◽  
Product Life Cycle ◽  
Pharmacokinetic Profile ◽  
Oral Dosage ◽  
Fixed Dose ◽  
Pharmaceutical Ingredients ◽  
Delayed Release ◽  
Dose Combination ◽  
Compression Coating

The Pharmaceutical industry has become more interested in developing fixed-dose combinations (FDCs) in recent years. FDCs have been used successfully in a variety of clinical areas, including diabetes, HIV/AIDS,and cardiovascular diseases etc. FDCs are intended to extend the product life cycle and enhance patient compliance by decreasing cost. Active Pharmaceutical ingredients are chosen for FDC development based on variety of purposes such as Pharmacokinetic profile, drug-drug interactions, mechanism of action, and manufacturability for successful development. Tablet in tablet technology has gained popularity in recent years for creating modified release products. The compression coating or solvent-free-coating technology is also known as Tablet in Tablet technology. Tablet in Tablet technology is presently the finest alternative technology for the formulation of bilayer tablets for physical separation of active medicines and used to avoid chemical incompatibilities and to produce different drug release patterns such as rapid release, sustained release, controlled release, delayed release, and pulsatile release. This review mainly focuses on combining the techniques of both FDC and Tablet in Tablet formulations which offer a wide variety of benefits such as increased patient compliance, convenience, separation of incompatible ingredients, avoiding close interaction of two drugs, achieving various drug release patterns and maximizing the potency of both drugs over conventional oral dosage forms Keywords: Fixed dose combinations, Tablet in tablet technology, Compression coated tablet, Bilayer tablet, delayed release

The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy

2021 ◽  
pp. 1-11
Author(s):  
David I. Finkelstein ◽  
Jay J. Shukla ◽  
Robert A. Cherny ◽  
Jessica L. Billings ◽  
Eiman Saleh ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Pharmacokinetic Profile ◽  
Alpha Synuclein ◽  
Redox Activity ◽  
Substantia Nigra Pars Compacta ◽  
Drug Candidate ◽  
Older Volunteers ◽  
Control Food ◽  
Alpha Synuclein Aggregation

Background: An elevation in iron levels, together with an accumulation of α-synuclein within the oligodendrocytes, are features of the rare atypical parkinsonian disorder, Multiple System Atrophy (MSA). We have previously tested the novel compound ATH434 (formally called PBT434) in preclinical models of Parkinson’s disease and shown that it is brain-penetrant, reduces iron accumulation and iron mediated redox activity, provides neuroprotection, inhibits alpha synuclein aggregation and lowers the tissue levels of alpha synuclein. The compound was also well-tolerated in a first-in-human oral dosing study in healthy and older volunteers with a favorable, dose-dependent pharmacokinetic profile. Objective: To evaluate the efficacy of ATH434 in a mouse MSA model. Methods: The PLP-α-syn transgenic mouse overexpresses α-synuclein, demonstrates oligodendroglial pathology, and manifests motor and non-motor aspects of MSA. Animals were provided ATH434 (3, 10, or 30 mg/kg/day spiked into their food) or control food for 4 months starting at 12 months of age and were culled at 16 months. Western blot was used to assess oligomeric and urea soluble α-synuclein levels in brain homogenates, whilst stereology was used to quantitate the number of nigral neurons and glial cell inclusions (GCIs) present in the substantia nigra pars compacta. Results: ATH434 reduced oligomeric and urea soluble α-synuclein aggregation, reduced the number of GCIs, and preserved SNpc neurons. In vitro experiments suggest that ATH434 prevents the formation of toxic oligomeric species of synuclein. Conclusion: ATH434 is a promising small molecule drug candidate that has potential to move forward to trial for treating MSA.

scholarly journals Contribution to the Improvement of an Oral Formulation of Niclosamide, an Antihelmintic Drug Candidate for Repurposing in SARS-CoV-2 and Other Viruses

2020 ◽  
Author(s):  
Eduardo José Barbosa ◽  
Mariana Ribeiro Gubitoso ◽  
Nádia Araci Bou-Chacra ◽  
Stephen R. Byrn ◽  
Flavio M. S. Carvalho ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Aqueous Solubility ◽  
Oral Formulation ◽  
Oral Dosage ◽  
Drug Candidate ◽  
Formulation Development ◽  
Polymer Dispersions ◽  
Kinetic Solubility ◽  
Oral Dosage Forms

<p>Niclosamide (NCL) is an effective anthelmintic agent that has been shown to possess broad-spectrum antiviral activity, including against<b> </b>SARS-CoV-2. Due to its poor solubility in aqueous medium, however, the commercially available NCL formulations can act only locally in gastrointestinal worms and are not suitable to achieve plasmatic levels to treat systemic diseases. Consequently, the repurposing of this drug represents a challenge for formulation development with serious risks to the biological availability and can compromise preclinical and clinical outcomes. Herein, we report possible formulation, through the research and development, of stable amorphous solid dispersions to improve its solubility. The results of exploratory screening of NCL-polymer dispersions (performed through X-ray powder diffraction and kinetic solubility studies) indicate that soluplus-niclosamide dispersions can increase its aqueous solubility and, consequently, have the potential to enhance NCL bioavailability. <a>This outcome can be used for the development of oral dosage forms for clinical trials in SARS-CoV-2 and other viruses. </a></p>

scholarly journals Risk factors associated with echinococcosis in Chinese general population: a meta-analysis and systematic review

2021 ◽  
Author(s):  
tiantian zhang ◽  
Bin Li ◽  
Yuying Liu ◽  
Shou Liu
Keyword(s):  
Risk Factors ◽  
Subgroup Analysis ◽  
Human Life ◽  
Meta Analysis ◽  
Test Results ◽  
Knowledge Infrastructure ◽  
Pooled Prevalence ◽  
Specific Subgroup ◽  
And Control ◽  
Chinese National Knowledge Infrastructure

Abstract Background Echinococcosis is a severe zoonotic disease that imposes a substantial burden on human life. Numerous studies on echinococcosis have involved a variety of risk factors, and it is difficult to evaluate the key risk factors. The objectives of this meta-analysis are to summarize available data on the prevalence of human echinococcosis and identify the key risk factors for echinococcosis. Methods Relevant studies were comprehensively searched in the PubMed, EMBASE, Web of Science, Cochrane, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP Information (VIP), Wanfang and SinoMed databases from database inception until August 22, 2020. A random-effects model was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI) by integrating the OR values of each risk factor. The I2 and Q statistics were calculated to evaluate the heterogeneity, and potential sources of heterogeneity were identified using sensitivity analysis and subgroup analysis. Publication bias was estimated by funnel plots and Egger’s test. Results A total of 1026 studies were identified through the database search, of which 26 were eligible for this meta-analysis. In total, 23 and 9 of the 26 studies were cystic echinococcosis (CE) and alveolar echinococcosis (AE) studies, respectively (6 papers included both AE and CE). The pooled prevalence of echinococcosis was 5.52% (95% CI: 5.47%-5.58%). Ethnicity (OR = 2.93, 95% CI: 1.81–4.75; I2 = 0), being a herder (OR = 2.66, 95%CI95% CI: 2.25–3.14; I2 = 8%), not washing hands before meals (OR = 2.40, 95% CI: 1.34–4.28; I2 = 82.8%) and being female (OR = 1.45, 95% CI: 1.26–1.66; I2 = 33.9%) were risk factors for AE. The top five risk factors for CE were ethnicity (OR = 3.18, 95% CI: 1.55–6.52; I2 = 79.2%), nomadism (OR = 2.71, 95% CI: 1.65–4.47; I2 = 55.8%), drinking nonboiled water (OR = 2.47, 95% CI: 1.36–4.47; I2 = 85.7), feeding viscera to dogs (OR = 2.35, 95% CI: 1.89–2.91; I2 = 21.5%), and being a herder (OR = 2.19, 95% CI: 1.67–2.86; I2 = 85.1%). The study design-specific subgroup analysis showed that the heterogeneity of CE risk factors decreased to varying degrees. Conclusions Specific characteristics (i.e., ethnicity and herder status) and behaviors (i.e., not washing hands before meals and feeding viscera to dogs ) are possible risk factors for echinococcosis. This study provided remarkable insight for future prevention and control of echinococcosis.

scholarly journals SEMANTIC ASPECT OF ARABIC MORPHOLOGY: IDEAS AND THEORIES/ وقفات دلالية في الصرف العربي أفكار و رؤى

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Abdulwahab Ajao Salaudeen
Keyword(s):  
Analytical Method ◽  
General View ◽  
Arabic Morphology ◽  
Semantic Element ◽  
Semantic Aspect ◽  
Shed Light

<p>This research aims to shed light on a semantic aspect of Arabic morphology; the study shows that Arabic morphologists emphasized formative aspect more than the grammatical element which made Arabic morphology difficult to comprehend, it has gone to the level of generalizing some rules without giving semantic element adequate attention. There is no doubt on the fact that the formative element of Arabic morphology has to go side by side with semantic aspect to simplify and clarify its study. However, this research points out the advantages of applying the theory of Semantic /Analytical Field for identifying the characteristics of each morphological forms. The researcher applies the descriptive and analytical method to give a general view of this morpho- semantic study.</p><p><strong></strong><strong>Keywords</strong>: Semantic; Arabic Morphology; Ideas; Visions</p>

D-alanine metabolism via D-Ala aminotransferase by marine Gammaproteobacteria , Pseudoalteromonas sp. CF6-2

2021 ◽  
Author(s):  
Yang Yu ◽  
Jie Yang ◽  
Zhao-Jie Teng ◽  
Li-Yuan Zheng ◽  
Qi Sheng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Marine Bacteria ◽  
Gene Knockout ◽  
Underlying Mechanism ◽  
Dominant Group ◽  
Seawater Samples ◽  
Underlying Mechanisms ◽  
Biochemical Analyses ◽  
Global Oceans ◽  
Shed Light

As the most abundant D-amino acid (DAA) in the ocean, D-alanine (D-Ala) is a key component of peptidoglycan in bacterial cell wall. However, the underlying mechanisms of bacterial metabolization of D-Ala through microbial food web remain largely unknown. In this study, the metabolism of D-Ala by marine bacterium Pseudoalteromonas sp. CF6-2 was investigated. Based on genomic, transcriptional and biochemical analyses combined with gene knockout, D-Ala aminotransferase was found to be indispensable for the catabolism of D-Ala in strain CF6-2. Investigation on other marine bacteria also showed that D-Ala aminotransferase gene is a reliable indicator for their ability to utilize D-Ala. Bioinformatic investigation revealed that D-Ala aminotransferase sequences are prevalent in genomes of marine bacteria and metagenomes, especially in seawater samples, and Gammaproteobacteria represents the predominant group containing D-Ala aminotransferase. Thus, Gammaproteobacteria is likely the dominant group to utilize D-Ala via D-Ala aminotransferase to drive the recycling and mineralization of D-Ala in the ocean. IMPORTANCE As the most abundant D-amino acid in the ocean, D-Ala is a component of marine DON (Dissolved organic nitrogen) pool. However, the underlying mechanism of bacterial metabolization of D-Ala to drive the recycling and mineralization of D-Ala in the ocean is still largely unknown. The results in this study showed that D-Ala aminotransferase is specific and indispensable for D-Ala catabolism in marine bacteria, and that marine bacteria containing D-Ala aminotransferase genes are predominantly Gammaproteobacteria widely distributed in global oceans. This study reveals marine D-Ala utilizing bacteria and the mechanism of their metabolization of D-Ala. The results shed light on the mechanisms of recycling and mineralization of D-Ala driven by bacteria in the ocean, which are helpful in understanding oceanic microbial-mediated nitrogen cycle.

scholarly journals Age at Menopause and Risk of Developing Endometrial Cancer: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Yanjun Wu ◽  
Wenjun Sun ◽  
Hui Liu ◽  
Dongfeng Zhang
Keyword(s):  
Endometrial Cancer ◽  
Dose Response ◽  
Meta Analysis ◽  
Positive Association ◽  
Response Analysis ◽  
Age At Menopause ◽  
Relative Risks ◽  
Knowledge Infrastructure ◽  
Study Heterogeneity ◽  
Chinese National Knowledge Infrastructure

Object. The association of age at menopause with endometrial cancer remains controversial. Therefore, we quantitatively summarized the evidence from observational studies with a meta-analysis. Methods. We searched PubMed, Web of Science, Embase, Medline, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang Med online up to March 2019, and all eligible case-control and cohort studies were included in the study. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random-effects model. The dose-response relationship was assessed by restricted cubic spline model. The heterogeneity among studies was evaluated by I2. Metaregression was used to explore the potential sources of between-study heterogeneity. Egger’s test was used to estimate publication bias. Results. Eighteen articles including 957242 subjects with 4781 cases were included in the meta-analysis. The pooled RR (95%CI) of endometrial cancer for the highest versus the lowest age at menopause was 1.89 (95%CI: 1.58-2.26). For dose-response analysis, a nonlinear relationship was found between age at menopause and endometrial cancer, and the positive association became statistically significant when age at menopause was greater than 46.5 years old. Conclusions. This meta-analysis suggested that age at menopause was positively associated with endometrial cancer. For women whose menopausal age over 46.5 years old, the risk of endometrial cancer increased with the age at menopause.

scholarly journals Clinical Effects and Safety of Electroacupuncture for the Treatment of Poststroke Dysphagia: A Comprehensive Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jinke Huang ◽  
Yao Shi ◽  
Xiaohui Qin ◽  
Min Shen ◽  
Manli Wu ◽  
...  
Keyword(s):  
Rating Scale ◽  
Meta Analysis ◽  
Effective Rate ◽  
Control Treatment ◽  
Sufficient Evidence ◽  
Cochrane Library ◽  
Clinical Effects ◽  
Knowledge Infrastructure ◽  
Swallowing Rehabilitation ◽  
Chinese National Knowledge Infrastructure

Objectives. Electroacupuncture (EA), an extension of acupuncture, which is based on traditional acupuncture combined with modern electrotherapy, is commonly used for poststroke dysphagia (PSD) in clinical treatment and research. However, there is still a lack of sufficient evidence to recommend the routine use of EA for PSD. The aim of this study was to assess the efficacy and safety of EA in the treatment of PSD. Methods. Randomized controlled trials (RCTs) evaluating the effects of EA on PSD were identified through a comprehensive literature search of the PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, and VIP databases from their inception to July 2020. The quality assessment of the included trials was performed based on the guidance of the Cochrane Reviewers’ Handbook, and meta-analysis (MA) was performed by using the RevMan 5.3 software. Results. Sixteen trials were identified, and these included 1,216 patients with PSD. The results demonstrated that EA in combination with swallowing rehabilitation training (SRT) was significantly superior to SRT alone with regard to effective rate (OR 5.40, 95% CI [3.78, 7.72], P < 0.00001 , water swallow test (WST) (MD −0.78, 95% CI [−1.07, −0.50], P < 0.00001 ), the video fluoroscopic swallowing study (VFSS) (MD 1.47, 95% CI [1.11, 1.84], P < 0.00001 ), the Ichiro Fujishima Rating Scale (IFRS) (MD 1.94, 95% CI [1.67, 2.22], P < 0.00001 ), and the incidence of aspiration pneumonia (IAP) (OR 0.20, 95% CI [0.06, 0.61], P = 0.005 ). Conclusions. The results showed that EA was better than the control treatment in terms of the effective rate, WST, VFSS, IFRS, and IAP of dysphagia after stroke. Strict evaluation standards and high-quality RCT designs are necessary for further exploration.

scholarly journals CD44 overexpression related to lymph node metastasis and poor prognosis of pancreatic cancer

2018 ◽  
Vol 33 (3) ◽  
pp. 308-313 ◽  
Author(s):  
Yijuan Liu ◽  
Ting Wu ◽  
Dong Lu ◽  
Jiantao Zhen ◽  
Lin Zhang
Keyword(s):  
Pancreatic Cancer ◽  
Lymph Node ◽  
Meta Analysis ◽  
Clinicopathological Features ◽  
Current Evidence ◽  
Overall Survival Rate ◽  
Node Metastasis ◽  
Knowledge Infrastructure ◽  
Chinese National Knowledge Infrastructure ◽  
Comprehensive Literature Search

Background: CD44 has recently been reported as a biomarker for pancreatic cancer. However, the predictive value of CD44 in pancreatic cancer remains controversial. Therefore, we performed this meta-analysis to evaluate the association between the expression of CD44 and clinicopathological features, and the outcome of pancreatic cancer patients. Materials and method: A comprehensive literature search was performed using PubMed, Embase, and Chinese National Knowledge Infrastructure. The statistical analysis was conducted using Stata software. Results: A total of nine studies including 583 cases were included in this meta-analysis. The meta-analysis indicated that CD44 overexpression was associated with poor five-year overall survival rate (OR 0.52; 95% CI 0.30, 0.91; P = 0.02), more lymph node invasion (OR 3.14 (positive vs. negative); 95% CI 1.47, 6.73; P = 0.003), more advanced T stage (OR 2.4 (T3,4 vs. T1,2); 95% CI 1.28, 4.52; P = 0.007), and more advanced TNM stage (OR 4.53 (III~IV vs. I~II); 95% CI 1.46, 14.08; P = 0.01). However, CD44 overexpression was not associated with other clinicopathological features, such as tumor size, differentiation, and distance metastasis. Conclusions: The current evidence suggests that CD44 is an efficient prognostic factor in pancreatic cancer.

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