Repositioning or "repurposing" of existing therapies for indications of alternative disease is an attractive approach that can generate lower costs and require a shorter approval time than developing a de novo drug. The development of experimental drugs is time-consuming, expensive, and limited to a fairly small number of targets. The incorporation of separate and complementary data should be used, as each type of data set exposes a specific feature of organism knowledge Drug repurposing opportunities are often focused on sporadic findings or on time-consuming pre-clinical drug tests which are often not guided by hypothesis. In comparison, repurposing in-silico drugs is a new, hypothesis-driven method that takes advantage of big-data use. Nonetheless, the widespread use of omics technology, enhanced data storage, data sense, machine learning algorithms, and computational modeling all give unparalleled knowledge of the methods of action of biological processes and drugs, providing wide availability, for both disease-related data and drug-related data. This review has taken an in-depth look at the current state, possibilities, and limitations of further progress in the field of drug repositioning.Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.The pathological characteristics of Parkinson's disease (PD) include dopaminergic neuron damage, specifically disorders caused by dopamine synthesis, in vivo. Plastrum testudinis extract (PTE) and its bioactive ingredient ethyl stearate (PubChem CID 8122) were reported to be correlated with tyrosine hydroxylase (TH), which is a biomarker of dopaminergic neurons. This suggests that PTE and its small-molecule active ingredient ethyl stearate have potential for development as a therapeutic drug for PD. In this study, we treated 6-hydroxydopamine (6-OHDA)-induced model rats and PC12 cells with PTE. The mechanism of action of PTE and ethyl stearate was investigated by western blotting, bisulfite sequencing PCR (BSP), real-time PCR, immunofluorescence and siRNA transfection. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html PTE effectively upregulated the TH expression and downregulated the alpha-synuclein expression in both the substantia nigra and the striatum of the midbrain in a PD model rat. The PC12 cell model showed that both PTE and its active monomer ethyl stearate significantly promoted TH expression and blocked alpha-synuclein, agreeing with the in vivo results. BSP showed that PTE and ethyl stearate increased the methylation level of the Snca intron 1 region. These findings suggest that some of the protective effects of PTE on dopaminergic neurons are mediated by ethyl stearate. The mechanism of ethyl stearate may involve disrupting the abnormal aggregation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) with alpha-synuclein by releasing DNMT1, upregulating Snca intron 1 CpG island methylation, and ultimately, reducing the expression of alpha-synuclein.
Neuroborreliosis is a rare cause of cerebral vasculitis and stroke. The incidence of Lyme borreliosis in Finland has been increasing in the last 20years, so we expect that Lyme neuroborreliosis-associated vasculitis can be a more common cause of stroke in the future.
We have retrospectively identified all adult patients (>16years old) diagnosed with borreliosis (A69.2 Lyme borreliosis), transient ischemic attack (TIA, G45), and ischemic stroke (I63) at Helsinki University Hospital during 1.1.2014-31.10.2019 at our neurological emergency department. Medical data and follow-up data were retrospectively collected from medical records. Neuroborreliosis was diagnosed according to the European Federation of Neurological Societies guidelines.
We have identified 10 cases of neuroborreliosis-associated stroke or TIA and/or vasculitis. Vasculitis as a manifestation of borreliosis was diagnosed in six patients of 1454 (0.4%) and stroke or TIA in nine (0.6%) of all borreliosis patients at Helsinki University Hospital. Clinical outcomes for all our patients were good with a modified Rankin scale (mRS) 0-2.
Lyme neuroborreliosis-associated vasculopathy and cerebrovascular events still remain rare but should be considered especially in Lyme borreliosis endemic areas. Prognosis is good with appropriate antibiotic treatment, but additional immunosupressive treatment is sometimes needed.
Lyme neuroborreliosis-associated vasculopathy and cerebrovascular events still remain rare but should be considered especially in Lyme borreliosis endemic areas. Prognosis is good with appropriate antibiotic treatment, but additional immunosupressive treatment is sometimes needed.
Whether tirofiban is safe and effective in cardioembolic stroke patients treated with endovascular thrombectomy (EVT) remains unknown; this study evaluated the safety and efficacy of low-dose tirofiban in this patients population.
This study was a prospective registry study. Patients with cardioembolic stroke undergoing EVT from January 2013 to December 2020 were treated with EVT alone or EVT plus low-dose tirofiban. The primary outcome was symptomatic intracerebral hemorrhage (sICH) prior to discharge. The secondary outcomes included reocclusion, in-hospital mortality, and 3-month functional outcomes.
Overall, 288 patients were recruited and 117 received low-dose tirofiban; 137 patients (47.6%) experienced ICH, 42 patients (14.6%) were sICH, and 23 patients (8%) were fatal ICH. Thirteen patients (11.1%) receiving tirofiban and 29 patients (17.0%) not receiving tirofiban experienced sICH (p= 0.167). Reocclusion occurred in nine patients (7.7%) receiving tirofiban and 15 patients (8.8%) not receiving tirofiban (p=0.
Repositioning or "repurposing" of existing therapies for indications of alternative disease is an attractive approach that can generate lower costs and require a shorter approval time than developing a de novo drug. The development of experimental drugs is time-consuming, expensive, and limited to a fairly small number of targets. The incorporation of separate and complementary data should be used, as each type of data set exposes a specific feature of organism knowledge Drug repurposing opportunities are often focused on sporadic findings or on time-consuming pre-clinical drug tests which are often not guided by hypothesis. In comparison, repurposing in-silico drugs is a new, hypothesis-driven method that takes advantage of big-data use. Nonetheless, the widespread use of omics technology, enhanced data storage, data sense, machine learning algorithms, and computational modeling all give unparalleled knowledge of the methods of action of biological processes and drugs, providing wide availability, for both disease-related data and drug-related data. This review has taken an in-depth look at the current state, possibilities, and limitations of further progress in the field of drug repositioning.Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.The pathological characteristics of Parkinson's disease (PD) include dopaminergic neuron damage, specifically disorders caused by dopamine synthesis, in vivo. Plastrum testudinis extract (PTE) and its bioactive ingredient ethyl stearate (PubChem CID 8122) were reported to be correlated with tyrosine hydroxylase (TH), which is a biomarker of dopaminergic neurons. This suggests that PTE and its small-molecule active ingredient ethyl stearate have potential for development as a therapeutic drug for PD. In this study, we treated 6-hydroxydopamine (6-OHDA)-induced model rats and PC12 cells with PTE. The mechanism of action of PTE and ethyl stearate was investigated by western blotting, bisulfite sequencing PCR (BSP), real-time PCR, immunofluorescence and siRNA transfection. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html PTE effectively upregulated the TH expression and downregulated the alpha-synuclein expression in both the substantia nigra and the striatum of the midbrain in a PD model rat. The PC12 cell model showed that both PTE and its active monomer ethyl stearate significantly promoted TH expression and blocked alpha-synuclein, agreeing with the in vivo results. BSP showed that PTE and ethyl stearate increased the methylation level of the Snca intron 1 region. These findings suggest that some of the protective effects of PTE on dopaminergic neurons are mediated by ethyl stearate. The mechanism of ethyl stearate may involve disrupting the abnormal aggregation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) with alpha-synuclein by releasing DNMT1, upregulating Snca intron 1 CpG island methylation, and ultimately, reducing the expression of alpha-synuclein.
Neuroborreliosis is a rare cause of cerebral vasculitis and stroke. The incidence of Lyme borreliosis in Finland has been increasing in the last 20years, so we expect that Lyme neuroborreliosis-associated vasculitis can be a more common cause of stroke in the future.
We have retrospectively identified all adult patients (>16years old) diagnosed with borreliosis (A69.2 Lyme borreliosis), transient ischemic attack (TIA, G45), and ischemic stroke (I63) at Helsinki University Hospital during 1.1.2014-31.10.2019 at our neurological emergency department. Medical data and follow-up data were retrospectively collected from medical records. Neuroborreliosis was diagnosed according to the European Federation of Neurological Societies guidelines.
We have identified 10 cases of neuroborreliosis-associated stroke or TIA and/or vasculitis. Vasculitis as a manifestation of borreliosis was diagnosed in six patients of 1454 (0.4%) and stroke or TIA in nine (0.6%) of all borreliosis patients at Helsinki University Hospital. Clinical outcomes for all our patients were good with a modified Rankin scale (mRS) 0-2.
Lyme neuroborreliosis-associated vasculopathy and cerebrovascular events still remain rare but should be considered especially in Lyme borreliosis endemic areas. Prognosis is good with appropriate antibiotic treatment, but additional immunosupressive treatment is sometimes needed.
Lyme neuroborreliosis-associated vasculopathy and cerebrovascular events still remain rare but should be considered especially in Lyme borreliosis endemic areas. Prognosis is good with appropriate antibiotic treatment, but additional immunosupressive treatment is sometimes needed.
Whether tirofiban is safe and effective in cardioembolic stroke patients treated with endovascular thrombectomy (EVT) remains unknown; this study evaluated the safety and efficacy of low-dose tirofiban in this patients population.
This study was a prospective registry study. Patients with cardioembolic stroke undergoing EVT from January 2013 to December 2020 were treated with EVT alone or EVT plus low-dose tirofiban. The primary outcome was symptomatic intracerebral hemorrhage (sICH) prior to discharge. The secondary outcomes included reocclusion, in-hospital mortality, and 3-month functional outcomes.
Overall, 288 patients were recruited and 117 received low-dose tirofiban; 137 patients (47.6%) experienced ICH, 42 patients (14.6%) were sICH, and 23 patients (8%) were fatal ICH. Thirteen patients (11.1%) receiving tirofiban and 29 patients (17.0%) not receiving tirofiban experienced sICH (p= 0.167). Reocclusion occurred in nine patients (7.7%) receiving tirofiban and 15 patients (8.8%) not receiving tirofiban (p=0.
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