High-throughput screening is a regular approach available for identitying new lead compounds for the growing validated drug targets in drug screening. However, it has also introduced a large number of peculiar molecules which interfere drug screening. Pan assay interference compounds (PAINS) interfere with the progress of drug screening in various ways, such as interfering with a biochemical assay, modifying the protein, aggregate-based inhibitors and so on. So it is of vital significance to remove them. This paper has consulted the concept, category of PAINS and reviewed the way of PAINS interfering and the countermeasures to cope with them to direct the approach of high through screening and improve the hits percent.
Drug Discovery ; High-Throughput Screening Assays ; methods

Thioredoxin-interacting protein (TXNIP), also known as vitamin D3-up-regulated protein (VDUP1), is an endogenous inhibitor of thioredoxin (Trx), which regulates the cellular reduction-oxidation (redox) state. TXNIP regulates cellular survival, apoptosis and inflammation induced by glucotoxicity, heat shock and mechanical pressure. The above functions of TXNIP are regulated by carbohydrate response element binding protein (ChREBP) and AMP-dependent protein kinase (AMPK). In recent years, numerous studies showed that TXNIP is involved in diabetes and diabetic complications. On the one hand, TXNIP functions in diabetes by increasing insulin resistance and hepatic gluconeogenesis. TXNIP expression is induced by high glucose, which is implicated in pancreatic beta cell glucotoxicity and endothelial cells dysfunction. TXNIP may contribute to the development and progression of diabetes and its vascular complications. TXNIP may be a new target for diabetes and its vascular complications therapy.
Apoptosis ; Carrier Proteins ; metabolism ; Diabetes Complications ; drug therapy ; metabolism ; Diabetes Mellitus ; drug therapy ; metabolism ; Endothelial Cells ; pathology ; Humans ; Inflammation ; Insulin Resistance ; Insulin-Secreting Cells ; pathology ; Vascular Diseases ; drug therapy ; metabolism

Most medicines used in the ancient people were the natural raw products, and most of them were discovered during the life.As the differences of the geography,climate and living habits among the different regions,various medicines were used for treatment of diseases in local people.The communica-tion of medicines made a lot of benefits for people living in different regions. Communication of medicines promote the application of medicines and natural resources.As early as 2000 year ago, the ancient Chinese people had sent a lot of medicines to many countries among the Belt and Road during their visiting to these countries. The medicines were the main contents for communication besides of the silk and porcelain.These medicines has been used for treatment of diseases for local people till now.On the Belt and Road, many spices, fruits, seeds produced in different regions were spread among the countries.Most of them were planted and produced in China.But the important events were the application of these special products, such as spices, fruits and seeds used as medicines under the guidance of traditional Chinese medical theory. These drugs have played major roles in the treatment of diseases and development of traditional Chinese medicine. Communication of the medicines, including the medical theory and drugs, improved the medical standards in China.For example,ancient Persian medicine had a significant impact on the use of tradi-tional Chinese medicine in the prescription application.And also, the medicines made important contri-butions to the health of people in the countries on the Belt and Road. Now, the science and techniques have been developed. Many principles and understandings are different from the ancient people. However, the medicines developed in the countries on the Belt and Road still used for the health of human beings.To research the ancient medicines by the modern tech-niques and through co-operation will greatly contribute to human healthand promote the social prog-ress and economic development of the countries on the Belt and Road.

Salvianolic acids are the main water-soluble active compounds of Salvia miltiorrhiza and have been widely used for the treatment of cardiovascular diseases. Based on the latest studies in China and abroad, we summarize the pharmacological effects and mechanism of salvianolic acids on ischemic heart disease by describing how salvianolic acid A and salvianolic acid B protect the vascular endothelium, relax coronary arteries, promote angiogenesis and anti-platelet aggregation, inhibit the inflammatory response, anti-cell apoptosis, and scavenge free radicals. This review provides a theoretical basis for further research on the effects of salvianolic acids on ischemic heart disease and their potential for drug development.

Ischemic heart disease (IHD), which has been considered to be exclusively caused by stenosis or occlusion of coronary artery, is a significant cause of morbidity and mortality worldwide. Mitochondrial dysfunction is the main pathological basis of ischemic heart disease and reperfusion injury, and moderate mitochondrial autophagy can selectively remove damage proteins and organelles to maintain intracellular homeostasis, so mitochondrial autophagy is important for maintaining the homeostasis of cardiomyocytes. Natural drugs from plants are widely used in ischemic heart disease. In recent years, more and more natural drugs have been proven to alleviate myocardial cell damage after ischemia/reperfusion through mitochondrial autophagy. This paper reviews the research progress of natural drugs from plants medicines regulating mitochondrial autophagy in the treatment of ischemia heart disease.

Diabetic nephropathy presents an increasing trend worldwide. It has been an attractive area to find novel targets for the treatment of diabetic nephropathy. SIRT1 (Sirtuin 1), a member of deacetylation enzymes, regulates cell senescence, metabolism, and apoptosis. In last ten years, lots of studies showed that SIRT1 exerts a protective effect in the progression of the diabetic nephropathy by promoting reconstruction of energy homeostasis, modulating cell redox state, resisting cell apoptosis, inhibiting inflammation and ameliorating renal fibrosis. SIRT1 has become a potential new target for the treatment of diabetic nephropathy.
Apoptosis ; Cellular Senescence ; Diabetic Nephropathies ; pathology ; Humans ; Oxidation-Reduction ; Sirtuin 1 ; physiology

Wound healing is a complex and highly regulated process to maintaining the skin barrier function. Wounds of diabetic patients are hard or even not healing. Non-healing diabetic foot ulcers can lead to lower-extremity amputations. Diabetic wound healing problem is the main complication that leads to high disability rate of diabetes and can threaten the lives in severe cases. The healing of skin wounds requires the synergy of multiple factors to restore the injured skin to its barrier function. The mechanisms that cause it difficult to heal diabetic wounds are complex, including oxidative stress, chronic inflammation, decreased neovascularization, peripheral neuropathy, and imbalance of extracellular matrix accumulation and remodeling. This review classifies mechanisms of diabetic wound healing and provides a reference for its further research.

Mitochondria play a key role in cell metabolism. In addition to synthesizing ATP, they also participate in many physiological and pathological processes, including apoptosis, inflammation, oxidative stress, neuronal disease, tumor development, and aging. Most gene transcription of mitochondrial proteins occurs in the nucleus, so the biogenesis of mitochondria and the maintenance of mitochondrial homeostasis mainly depend on the expression of nuclear genes (nDNA) and mitochondria-nucleus interactions. Conversely, mitochondria can affect the expression of nuclear genes through nuclear transcription factors, a process called mitochondrial retrograde signaling. This review summarizes the research progress on mitochondria-nucleus retrograde signaling and its regulation, including the ways by which mitochondria regulate nuclear genes and affect biological processes, and discusses new strategies for the treatment of diseases that involve mitochondrial retrograde signaling in disease pathology.

Objective To explore the correlation between diffuse neurogenic changes on electromyography and diagnosis of amyotrophic lateral sclerosis (ALS).Methods Retrospective study was performed based on database of motor neuron disorders collected from January,2002 to December,2008.The category of disease with diffuse neurogenic changes at the first examination was summarized.The electromyography (EMG) manifestation in ALS patients at the first examination and the results after follow-up were reviewed.The factors affecting EMG manifestation in ALS were analyzed with binary Logistic regression.Results In 298 patients with diffuse neurogenic changes on EMG,192 cases (64.4％ ) were diagnosed of ALS,36 ( 12.1％ ) progressive muscular atrophy,13 (4.4％ ) Kennedy' s disease,10 (3.4％)Hirayama disease,9 ( 3.0％ ) cervical spondylosis combined with lumbar spondylosis,6 ( 1.3％ ) spinal muscular disease,5 ( 1.7％ ) multifocal motor neuropathy,5 ( 1.7％ ) ALS-plus disease,4 ( 1.3％ )myopathy,3( 1.0％ ) hereditary motor neuropathy,3 ( 1.0％ ) axonal motor neuropathy,2(0.7％ ) postpolio syndrome,and 10 (3.4％) with no definite diagnosis.In total 213 patients who were diagnosed with ALS after follow-up,at their first examinations,8 (3.8％) had neurogenic changes in two regions and 13(6.1％ ) had neurogenic changes in one region,and they all developed to diffuse neurogenic changes after follow-up for 3 to 24 months.Logistic regression analysis showed that the EMG change at first examination was not related to duration from onset,symptom location at onset,age at onset and gender.Conclusion Diffuse neurogenic changes on EMG can present in many disease including ALS.Neurogenie changes in one or two regions on EMG can be the manifestation of ALS at early stage.

Objective To retrospectively analyze clinical manifestations of autonomic nervous system (ANS) and skin sympathetic response (SSR) in Lambert-Eaton myasthenic syndrome (LEMS).Methods Fifty-three LEMS patients' medical records were reviewed and information regarding clinical symptoms and signs of ANS and SSR testing results were collected.Results ( 1 ) The most common initial symptom of LEMS was weakness of lower extremities ( n =41 ) and the most common symptom of ANS dysfunction was constipation ( n =25 ) and dry-mouth ( n =23),which could be occurred before the onset of the legs (n =7).(2) In symptoms of ANS,cardiovascular system dysfunction was found in 4 patients include one of ingone of bradycardia,one of postural hypotension and 2 of tachycardia- Secretory glands dysfunction was found in 34 patients:23 dry-mouth,6 dry-eyes,and 8 patients sweating dysfunctions.Twenty-eight patients complained of alimentary dysfunction including constipation and diarrhea.Bladder dysfunction was found in 2 patients,who complained of urinary incontinence.Seven male patients complained of sexual dysfunction.Abnormal skin scratch test was found in 17 patients.(3) SSR was performed in 33 patients and 18 found abnormal.Conclusions ANS manifestations are common and prominent in LEMS patients.SSR abnormality is also common in LEMS.More electrophysiology tests are needed in LEMS patients.