AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver,pancreatic, and colorectal cancers.METHODS: The changes in serum levels of retinoids (vitamin A, α- and β...AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver,pancreatic, and colorectal cancers.METHODS: The changes in serum levels of retinoids (vitamin A, α- and β-carotene, α- and β-cryptoxanthin,zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC)and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21including 9 patients suffering from in situ colon cancer)cancer. Fifty-seven healthy subjects (in matched groups)for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used.RESULTS: The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of α- and β-carotene,α- and β-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer.CONCLUSION: Retinoids (as environmental factors)are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.展开更多
Background: Pharmacovigilance of biological medicines is crucial because it ensures that medicines meet the World Health Organization (WHO) standards. In Zambia, there is little information on healthcare professionals...Background: Pharmacovigilance of biological medicines is crucial because it ensures that medicines meet the World Health Organization (WHO) standards. In Zambia, there is little information on healthcare professionals’ familiarity, knowledge and practices on the pharmacovigilance of biological and biosimilar medicines. Therefore, this study investigated the familiarity, knowledge, and practices related to the pharmacovigilance (PV) of biological and biosimilar medicines at selected hospitals in Lusaka, Zambia. Methods: The study was an analytical questionnaire-based cross-sectional study conducted among healthcare professionals (HCPs) at the Adult hospital, Cancer Diseases hospital, Paediatrics hospital and Women and New Born Hospital in Lusaka. Data were collected over four weeks in May and June 2021 and subsequently analysed using IBM SPSS version 21. The statistical significance was set at a 95% confidence interval. Results: Of 245 participants, only 115 (48.9%) of the HCPs were familiar with biological medicines to a basic understanding. Regarding the term biosimilars, most of the HCPs (40.9%) never heard of this word. The mean score for knowledge regarding the PV considerations of biological medicines was 4.1 out of 8 questions. Most HCPs used non-proprietary names (44.2%) when prescribing, dispensing, or administering biological medicines. Additionally, more than half (57.3%) of HCPs did not record batch numbers when dispensing or administering biological medicines. Conclusion: Healthcare professionals were more familiar with the term biological medicines than biosimilars. Healthcare professionals generally scored poorly when their knowledge regarding the PV considerations of biological medicines was assessed. Thus, there is a need to provide adequate training and continuous professional development among healthcare professionals on the pharmacovigilance of biological and biosimilar medicines.展开更多
The striatum is the primary input structure of the basal ganglia, which participates in motivational and goaldirected behaviors(Pisani et al., 2007).In physiological conditions, local cholinergic interneurons(ChIs) an...The striatum is the primary input structure of the basal ganglia, which participates in motivational and goaldirected behaviors(Pisani et al., 2007).In physiological conditions, local cholinergic interneurons(ChIs) and dopaminergic afferents modulate basal ganglia output through striatal projection neurons.展开更多
Insufficient dietary intake of micronutHents, known as ＂hidden hunger＂, is a devastating global burden, affecting two billion people. Deficiency of folates （vitamin B9）, which are known to play a central role in C...Insufficient dietary intake of micronutHents, known as ＂hidden hunger＂, is a devastating global burden, affecting two billion people. Deficiency of folates （vitamin B9）, which are known to play a central role in Cl metabolism, causes birth defects in at least a quarter million people annually. Biofortification to enhance the level of naturally occurring folates in crop plants, proves to be an efficient and cost-effective tool in fighting folate deficiency. Previously, introduction of folate biosynthesis genes GTPCHI andADCS, proven to be a successful biofortification strategy in rice and tomato, turned out to be insufficient to adequately increase folate levels in potato tubers. Here, we provide a proof of concept that additional introduction of HPPK/DHPS and/or FPGS, downstream genes in mitochonddal folate biosynthesis, enables augmenta- tion of folates to satisfactory levels （12-fold） and ensures folate stability upon long-term storage of tubers. In conclusion, this engineering strategy can serve as a model in the creation of folate-accumulating potato cultivars, readily applicable in potato-consuming populations suffedng from folate deficiency.展开更多
A remarkable study by Guo et al.,published in Cell,suggests a compelling new direction for improving pain management:biased allosteric modulation of the neurotensin receptor 1(NTSR1),using the drug-like molecule SBI-8...A remarkable study by Guo et al.,published in Cell,suggests a compelling new direction for improving pain management:biased allosteric modulation of the neurotensin receptor 1(NTSR1),using the drug-like molecule SBI-810,promotesβ-arrestin2(βarr2)recruitment while avoiding canonical G protein signaling–thereby providing robust analgesia across a plethora of rodent models of both acute and chronic pain without impairing motor function,cognition,or causing opioid-like dependency.1,2 SBI-810 is introduced as a highly promising molecule underscoring the therapeutic potential of biased and allosteric G protein-coupled receptor(GPCR)ligands to address an urgent unmet medical need.展开更多
基金Supported by the grant from the Hungarian Ministry of Health(ETT 595/2003)
文摘AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver,pancreatic, and colorectal cancers.METHODS: The changes in serum levels of retinoids (vitamin A, α- and β-carotene, α- and β-cryptoxanthin,zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC)and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21including 9 patients suffering from in situ colon cancer)cancer. Fifty-seven healthy subjects (in matched groups)for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used.RESULTS: The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of α- and β-carotene,α- and β-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer.CONCLUSION: Retinoids (as environmental factors)are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.
文摘Background: Pharmacovigilance of biological medicines is crucial because it ensures that medicines meet the World Health Organization (WHO) standards. In Zambia, there is little information on healthcare professionals’ familiarity, knowledge and practices on the pharmacovigilance of biological and biosimilar medicines. Therefore, this study investigated the familiarity, knowledge, and practices related to the pharmacovigilance (PV) of biological and biosimilar medicines at selected hospitals in Lusaka, Zambia. Methods: The study was an analytical questionnaire-based cross-sectional study conducted among healthcare professionals (HCPs) at the Adult hospital, Cancer Diseases hospital, Paediatrics hospital and Women and New Born Hospital in Lusaka. Data were collected over four weeks in May and June 2021 and subsequently analysed using IBM SPSS version 21. The statistical significance was set at a 95% confidence interval. Results: Of 245 participants, only 115 (48.9%) of the HCPs were familiar with biological medicines to a basic understanding. Regarding the term biosimilars, most of the HCPs (40.9%) never heard of this word. The mean score for knowledge regarding the PV considerations of biological medicines was 4.1 out of 8 questions. Most HCPs used non-proprietary names (44.2%) when prescribing, dispensing, or administering biological medicines. Additionally, more than half (57.3%) of HCPs did not record batch numbers when dispensing or administering biological medicines. Conclusion: Healthcare professionals were more familiar with the term biological medicines than biosimilars. Healthcare professionals generally scored poorly when their knowledge regarding the PV considerations of biological medicines was assessed. Thus, there is a need to provide adequate training and continuous professional development among healthcare professionals on the pharmacovigilance of biological and biosimilar medicines.
基金supported by the Fonds Wetenschappelijk Onderzoek(FWOSBO, Grant number 140028)Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación/FEDER(Grant number SAF2017-87349-R)+3 种基金Generalitat de Catalunya(Grant numbers 2017 SGR1604 and 2017 SGR595)Fundació la Marató de TV3(grant number 20152031)supported by an FWO Travel Grant for a Long Stay Abroad(grant number V420718N)an EMBO Short-Term Fellowship(grant number 6735)。
文摘The striatum is the primary input structure of the basal ganglia, which participates in motivational and goaldirected behaviors(Pisani et al., 2007).In physiological conditions, local cholinergic interneurons(ChIs) and dopaminergic afferents modulate basal ganglia output through striatal projection neurons.
文摘Insufficient dietary intake of micronutHents, known as ＂hidden hunger＂, is a devastating global burden, affecting two billion people. Deficiency of folates （vitamin B9）, which are known to play a central role in Cl metabolism, causes birth defects in at least a quarter million people annually. Biofortification to enhance the level of naturally occurring folates in crop plants, proves to be an efficient and cost-effective tool in fighting folate deficiency. Previously, introduction of folate biosynthesis genes GTPCHI andADCS, proven to be a successful biofortification strategy in rice and tomato, turned out to be insufficient to adequately increase folate levels in potato tubers. Here, we provide a proof of concept that additional introduction of HPPK/DHPS and/or FPGS, downstream genes in mitochonddal folate biosynthesis, enables augmenta- tion of folates to satisfactory levels （12-fold） and ensures folate stability upon long-term storage of tubers. In conclusion, this engineering strategy can serve as a model in the creation of folate-accumulating potato cultivars, readily applicable in potato-consuming populations suffedng from folate deficiency.
基金funding by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under DFG DE 1546/12-1(M.D.),559839626(M.D.),and 538291523(S.A.M.S.)funding from Ghent University BOF program grant number BOF23/PDO/073funding enabled and organized by Projekt DEAL.
文摘A remarkable study by Guo et al.,published in Cell,suggests a compelling new direction for improving pain management:biased allosteric modulation of the neurotensin receptor 1(NTSR1),using the drug-like molecule SBI-810,promotesβ-arrestin2(βarr2)recruitment while avoiding canonical G protein signaling–thereby providing robust analgesia across a plethora of rodent models of both acute and chronic pain without impairing motor function,cognition,or causing opioid-like dependency.1,2 SBI-810 is introduced as a highly promising molecule underscoring the therapeutic potential of biased and allosteric G protein-coupled receptor(GPCR)ligands to address an urgent unmet medical need.
