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@#The rapid spread of Coronavirus Disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has had a devastating impact on public health and the global economy. Tremendous efforts had been put on urgent development of prophylactic or therapeutic drugs against SARS-CoV-2,mainly smallmolecule antiviral drugs and monoclonal antibodies,to reduce the impact and burden of COVID-19. Currently,National Medical Products Administration(NMPA)of China or Food and Drug Administration(FDA)of the United States have approved three small-molecule drugs and three monoclonal antibodies for use. This paper reviews the clinical research progress and challenges of the main drugs against SARS-CoV-2 on the market at present.
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OBJECTIVE To review economic studies of diabetes drugs in Chinese population systematically ，and to provide reference for promoting the development of pharmacoeconomics research in the field of diabetes and improving the research quality. METHODS Retrieving from PubMed ，Embase，SinoMed，CNKI，Wanfang data ，VIP and other databases ，the literatures on economic evaluation of diabetes drugs in Chinese population were collected ；analysis was carried out on the publication ，research content，study design of the literatures. The Consolidated Health Economic Evaluation Reporting Standards 2013（CHEERS 2013） checklist was used for quality evaluation. RESULTS A total of 380 literatures were included ，involving 348 Chinese literatures and 32 English literatures. The first paper of diabetes drugs in Chinese population was published in 2001. The most evaluated drug was metformin. Most of the studies （79.2％）were conducted by medical institutions ，73.9％ of the studies were short-term economic evaluation，and the methods were mainly cost-effectiveness analysis （61.8％），and most of the studies did not reported clear research perspectives （82.6％）. Evaluated by CHEERS 2013，the average score of included literatures was only 10.57，and 85.8％ of the literatures was of unqualified quality. The average score of Chinese literatures was 10.05，that of English literatures was 16.23，and the reporting quality of English literatures was significantly better than that of Chinese literature s（P＜0.001）. CONCLUSIONS The existing literatures on the economic evaluation of diabetes drugs in Chinese population is of low quality. There are problems such as lack of research perspectives ，single research institution/method ，and non-standard reporting. It is recommended that medical institutions ，universities/research institutions ，enterprises，government and other institutions should strengthen cooperation ，improve their research level ，pay attention to more and newer clinically effective treatment regimens ，and promote the transformation of research results into decision-making evidence.
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@#Alzheimer''s disease (AD) is the most common cause of senile dementia, accounting for an estimated 60% to 80% of cases, but there are no approved drugs to slow or stop the progressive clinical decline in the past years.Amyloid cascade hypothesis is recognized as the major etiologic basis for AD, however, the failures of several amyloid plaque-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. Several reports show that soluble oligomers of Aβ (AβOs), which appear in brains more than 10 years before the clinical syndrome, are more toxic than Aβ plaque, causing synaptic dysfunction and neuronal apoptosis. Some agents that can effectively inhibit Aβ oligomer formation or block their toxicity made significant efficacy in clinical 2 and 3 trials, with the potential to be approved for the treatment of AD. This article reviews the recent development of AD drugs targeting Aβ oligomers, analyzes their structural characteristics, mechanism of action, preclinical and clinical data, and discusses the future direction of AD treatment, thus providing new strategies for AD drug research.
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Neuropathic pain(NPP)has always been a problem that puzzles the medical community because of its unclear pathogenesis and poor drug treatment. With the development of molecular biology and electrophysiological techniques, studies have shown that the complex pathological mechanism of NPP may be related to the activation of transient receptor potential vanillic acid sub-type 1(TRPV1). TRPV1 receptors are mainly expressed in peripheral sensory neurons, which can detect harmful stimuli in the external and internal environment and transmit information to the central nervous system, thereby playing an important role in peripheral neuropathic pain. TRPV1 modulators exert analgesic effects by blocking the pain transmission function of TRPV1 and have become a potential therapeutic agent in the treatment of NPP. This article reviews TRPV1 receptor-mediated NPP models and the role of TRPV1 modulators in NPP treatment.
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Bispecific antibody (BsAbs) are antibodies (Abs) containing two different antigen-binding sites in one molecule. In the last decade, three BsAbs drugs have been approved for therapeutic use. Meanwhile there are a number of BsAbs in preclinical or clinical studies. In this review, we describe BsAb design, discovery, mechanism of action, and the recent research progress in developing BsAbs.
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Man consumes drug for various medical and non-medical reasons. There are innumerable incidents where these medicines played havoc on humankind. If they are boon to man, they are also afflicting diseases. But, what about human drugs when they have an effect on environment? There has been growing concern among scientists and environmentalists about the vast amount of drugs that end up in the environment one way or another. Adverse consequences of drugs may influence socio-economic environment. Low levels of human medicines (pharmaceuticals) have been detected in many countries in sewage treatment plant (STP) effluents, surface waters, seawaters, groundwater and some drinking waters. For some pharmaceuticals effects on aquatic organisms have been investigated in acute toxicity assays but the chronic toxicity and potential subtle effects are only marginally known.
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The high-fidelity prostate tumor patient-derived xenograft ( PDX) model is the basis for studies of biology and pharmacotherapy of prostate cancer. However, the development and application of prostate tumor has been hampered by a low success rate of transplanted primary tumors in mice as most prostate cancers are highly relevant to hormones. The high-fidelity PDX model of prostate cancer better maintains the histopathology and molecular heterogeneity of the original tumor. Here, we review the improved method of establishing PDX model of prostate cancer, including the testosterone supplementation, the quality of the original tumor tissue as well as the stromal niche, and the application of commonly used therapeutic drugs, and to provide a theoretical basis for clinical studies of prostate tumor. These attempts are very important for development of new agents and research on mechanisms of prostate cancer. It will further promote the individualized treatment of prostate cancer.
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The demand for rapid and broad clinical toxicology screens is on the rise. Recently, a new rapid toxicology screening test, the Triage TOX Drug Screen (Alere Inc., USA), which can simultaneously detect 11 drugs of abuse and therapeutic drugs with an instrument-read cartridge, was developed. In the present study, we evaluated the efficacy of this new on-site immunoassay using 105 urine specimens; the results were compared with those obtained by using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-TMS). Precision was evaluated according to the CLSI EP12-A2 for analyte concentrations near the cutoff, including C₅₀ and±30% of C₅₀, for each drug using standard materials. The C₅₀ specimens yielded 35–65% positive results and the ±30% concentration range of all evaluated drugs encompassed the C₅–C₉₅ interval. The overall percent agreement of the Triage TOX Drug Screen was 92.4–100% compared with UPLC-TMS; however, the Triage TOX Drug Screen results showed some discordant cases including acetaminophen, amphetamine, benzodiazepine, opiates, and tricyclic antidepressants. The overall performance of the Triage TOX Drug Screen assay was comparable to that of UPLC-TMS for screening of drug intoxication in hospitals. This assay could constitute a useful screening method for drugs of abuse and therapeutic drugs in urine.
Subject(s)
Acetaminophen , Amphetamine , Antidepressive Agents, Tricyclic , Benzodiazepines , Chromatography, Liquid , Immunoassay , Mass Screening , Methods , Illicit Drugs , Tandem Mass Spectrometry , Toxicology , TriageABSTRACT
Tuberculosis (TB) is a symbolic menace to mankind, infecting almost one third of the world's populace and causing over a million mortalities annually. Mycobacterium tuberculosis (Mtb) is the key pathogen of TB that invades and replicates inside the host's macrophage. With the emerging dilemma of multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the exigency for developing new TB drugs is an obligation now for worldwide researchers. Among the propitious antimycobacterial agents examined in last few decades, anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity, selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action. In this review, we epitomized the current advances in the anti-tubercular peptides, focusing the sources and highlighting the mycobactericidal mechanisms of promising peptides. The review investigates the current anti-tubercular peptides exploited not only from human immune cells, human non-immune cells, bacteria and fungi but also from venoms, cyanobacteria, bacteriophages and several other unplumbed sources. The anti-tubercular peptides of those origins are also known to have unique second non-membrane targets within Mtb. The present context also describes the several cases that manifested the severe side effects of extant anti-TB drugs. The downfall, failure to reach clinical trial phases, inept to MDR- or XDR-TB and severe complications of the currently available anti-tubercular drugs accentuate the imperative necessity to develop efficacious drugs from adequate anti-tubercular peptides. Keeping in view of the emerging trends of drug resistant Mtb globally and unexampled mycobactericidal characteristics of peptides, the anti-tubercular peptides of varied origins can be used as a potential weapon to eradicate TB in future by developing new therapeutic drugs.
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Tuberculosis (TB) is a symbolic menace to mankind, infecting almost one third of the world's populace and causing over a million mortalities annually. Mycobacterium tuberculosis (Mtb) is the key pathogen of TB that invades and replicates inside the host's macrophage. With the emerging dilemma of multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the exigency for developing new TB drugs is an obligation now for worldwide researchers. Among the propitious antimycobacterial agents examined in last few decades, anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity, selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action. In this review, we epitomized the current advances in the anti-tubercular peptides, focusing the sources and highlighting the mycobactericidal mechanisms of promising peptides. The review investigates the current anti-tubercular peptides exploited not only from human immune cells, human non-immune cells, bacteria and fungi but also from venoms, cyanobacteria, bacteriophages and several other unplumbed sources. The anti-tubercular peptides of those origins are also known to have unique second non-membrane targets within Mtb. The present context also describes the several cases that manifested the severe side effects of extant anti-TB drugs. The downfall, failure to reach clinical trial phases, inept to MDR- or XDR-TB and severe complications of the currently available anti-tubercular drugs accentuate the imperative necessity to develop efficacious drugs from adequate anti-tubercular peptides. Keeping in view of the emerging trends of drug resistant Mtb globally and unexampled mycobactericidal characteristics of peptides, the anti-tubercular peptides of varied origins can be used as a potential weapon to eradicate TB in future by developing new therapeutic drugs.
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Lung cancer is ranked the first among all malignant neoplastic diseases because of its high morbidity and mortality rate. Thus, lung cancer seriously threatens human health. More than 80%of lung cancer cases are non-small cell lung cancer (NSCLC). Unfortunately, the majority of NSCLC patients are already at the terminal stage of the disease when they seek medical attention. Such patients miss the optimal opportunity of surgery;thus, medical treatment becomes the main choice for them. Recently, molecular-target-ed therapy has made tremendous progress in clinical practice and provides a new potential treatment for patients at the terminal stage. In this review, the authors introduced some molecular-targeted therapeutic drugs to provide benefits for the individualized treatment of patients.
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The Ebola virus was identified in the year 1976 and has caused periodic outbreaks in West African countries. The disease has a case fatality rate up to 90%. Ebola has been classified as a biosafety level four pathogen and there is no currently approved vaccine or treatment for the virus. However, remarkable progress has been demonstrated by researchers in understanding the pathogenicity of the Ebola virus. Several animal models have been cultivated to develop diagnostics, vaccines and therapeutic drugs.
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The Ebola virus was identified in the year 1976 and has caused periodic outbreaks in West African countries. The disease has a case fatality rate up to 90%. Ebola has been classified as a biosafety level four pathogen and there is no currently approved vaccine or treatment for the virus. However, remarkable progress has been demonstrated by researchers in understanding the pathogenicity of the Ebola virus. Several animal models have been cultivated to develop diagnostics, vaccines and therapeutic drugs.
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Functional dyspepsia is a common functional gastrointestinal disease , however , the cause of functional dyspepsia has not been fully elucidated .Ghrelin is braingut petide , secreted by major endocrine cells of the stomach ( x/A like cells ) .Its recep-tor is widely distributed in the body .It has many kinds of biological effects , such as regulating growth hormone secretion , feeding and energy balance , affecting neuroendocrine and gastrointestinal function and so on .A growing number of studies have shown that Ghrelin in FD has a positive role in increasing the improvement of food intake and generating hunger , promoting gastric emptying .Ghrelin is a new hot spot in the research of FD .
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West Nile virus is a single stranded RNA virus and belongs to the genus of Flavivirus. Human infections of West Nile virus can cause severe infectious diseases such as West Nile fever and West Nile encephalitis which seriously threaten human life. Up to now, there is still lack of effective vaccines and antiviral drugs against West Nile virus. Therefore, to develop effective drugs for the prevention and treatment of West Nile virus disease is of great importance to protecting human health and maintaining national securities. Herein, the research advances of biological characteristics, epidemiology, clinical symptoms, vaccine and therapeutic drugs of the West Nile virus are reviewed.