Pub Date : 2021-06-29DOI: 10.14218/jerp.2021.00012
A. Cardoso
The incidence of diabetes has been increasing dramatically in recent years, and diabetes remains a severe threat to global health. Herein, the updated viewpoint regarding the potential impact of gut microbiota on type 2 diabetes mellitus (T2DM) is discussed, and it is emphasized that standardized methods are essential for future studies.
{"title":"Can Changes in Gut Microbiota Predict Progression Toward Diabetes?","authors":"A. Cardoso","doi":"10.14218/jerp.2021.00012","DOIUrl":"https://doi.org/10.14218/jerp.2021.00012","url":null,"abstract":"The incidence of diabetes has been increasing dramatically in recent years, and diabetes remains a severe threat to global health. Herein, the updated viewpoint regarding the potential impact of gut microbiota on type 2 diabetes mellitus (T2DM) is discussed, and it is emphasized that standardized methods are essential for future studies.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44403234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-01DOI: 10.14218/JERP.2021.00004
Gong Feng, Lanjing Zhang, Ke Wang, Bohao Chen, H. Xia
The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the most formidable challenge to humanity in this century. The research and development of COVID-19 vaccines, which are believed to be the most effective tools to control this pandemic, has been a topic of critical importance, not only in the field of biomedicine but also in the entire international community. Here, we introduce the concepts related to COVID-19 vaccines, including their development process, clinical trials, designs and types. On this basis, we further summarize the research, development, and application of vaccines in different regions of the world, and describe the vaccines according to their respective regions. Finally, we discuss existing and emerging challenges, strategies and prospects of in the development and application of COVID-19 vaccines.
{"title":"Research, Development and Application of COVID-19 Vaccines: Progress, Challenges, and Prospects","authors":"Gong Feng, Lanjing Zhang, Ke Wang, Bohao Chen, H. Xia","doi":"10.14218/JERP.2021.00004","DOIUrl":"https://doi.org/10.14218/JERP.2021.00004","url":null,"abstract":"The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the most formidable challenge to humanity in this century. The research and development of COVID-19 vaccines, which are believed to be the most effective tools to control this pandemic, has been a topic of critical importance, not only in the field of biomedicine but also in the entire international community. Here, we introduce the concepts related to COVID-19 vaccines, including their development process, clinical trials, designs and types. On this basis, we further summarize the research, development, and application of vaccines in different regions of the world, and describe the vaccines according to their respective regions. Finally, we discuss existing and emerging challenges, strategies and prospects of in the development and application of COVID-19 vaccines.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44021059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-01DOI: 10.14218/JERP.2020.00043
K. Lawson, A. Singh, Ilya Kantsedikas, C. Jenner, Daniel Keith Austen
exhibits indirect N-methyl-D-aspartate (NMDA) receptor antagonism via activation of potassium channels, leading to the suppression of neuronal overex-citability. 3,4 Thus, flupirtine has been used as an analgesic for the last 35 years in the management of pain and also exerts skeletal muscle relaxation and neuroprotection properties. 3–5 Flupirtine is available as the maleate salt, a hydrophilic compound that is rap-idly absorbed from the gastrointestinal tract with a bioavailability of 90%. 6,7 The volume of distribution (Vd) of 100 mg of flupirtine is 154 L in healthy volunteers and is up to 84% bound to human albumin. 6,7 The half-life of flupirtine depends on the route of administration, but is typically between 6.5–10.7 h. Following oral administration of 100 mg of flupirtine, clearance is 275 ml/min in healthy volunteers. 6,7 Flupirtine is metabolized in the liver by per-Flupirtine Abstract Fibromyalgia is a complex disorder characterised by chronic pain, fatigue, sleep disturbance and cognitive dys-function with limited benefit gained with current therapies. The mean global prevalence of 2.7% is estimated for this chronic condition. Pharmacological and non-pharmacological therapeutic approaches are often required as treatments of the challenges associated with fibromyalgia. Flupirtine, a non-opioid drug, exhibits effective analgesia in a range of acute and persistent pain conditions, and evidence as treatment of fibromyalgia is considered. Activation of Kv7 potassium channels and agonism at gamma-aminobutyric acid receptor A leading to indirect N-methyl-D-aspartate receptor antagonism is responsible for the analgesic effects of flupirtine and appears to be involved in other symptoms associated with fibromyalgia. Patients with fibromyalgia reported improved control of their symptoms without significant adverse effects in an observational audit in clinical practice. This article presents evidence that flupirtine, or related drugs, is a therapeutic option for the treatment of fibromyalgia. The pharmacology of flupirtine and mechanisms of action involved provide a spectrum of effects that would not only control the chronic pain characteristic of fibromyalgia but many of the other symptoms. Thus, further investigation of the efficacy of flupirtine or related drugs exhibiting a similar pharmacology as a treatment of fibromyalgia would be of interest. oxidase enzymes to the active N-acetylated analogue D13223 and 4-fluorohippuric, which are further oxidised and then conjugated inactive metabolites.
{"title":"Flupirtine as a Potential Treatment for Fibromyalgia","authors":"K. Lawson, A. Singh, Ilya Kantsedikas, C. Jenner, Daniel Keith Austen","doi":"10.14218/JERP.2020.00043","DOIUrl":"https://doi.org/10.14218/JERP.2020.00043","url":null,"abstract":"exhibits indirect N-methyl-D-aspartate (NMDA) receptor antagonism via activation of potassium channels, leading to the suppression of neuronal overex-citability. 3,4 Thus, flupirtine has been used as an analgesic for the last 35 years in the management of pain and also exerts skeletal muscle relaxation and neuroprotection properties. 3–5 Flupirtine is available as the maleate salt, a hydrophilic compound that is rap-idly absorbed from the gastrointestinal tract with a bioavailability of 90%. 6,7 The volume of distribution (Vd) of 100 mg of flupirtine is 154 L in healthy volunteers and is up to 84% bound to human albumin. 6,7 The half-life of flupirtine depends on the route of administration, but is typically between 6.5–10.7 h. Following oral administration of 100 mg of flupirtine, clearance is 275 ml/min in healthy volunteers. 6,7 Flupirtine is metabolized in the liver by per-Flupirtine Abstract Fibromyalgia is a complex disorder characterised by chronic pain, fatigue, sleep disturbance and cognitive dys-function with limited benefit gained with current therapies. The mean global prevalence of 2.7% is estimated for this chronic condition. Pharmacological and non-pharmacological therapeutic approaches are often required as treatments of the challenges associated with fibromyalgia. Flupirtine, a non-opioid drug, exhibits effective analgesia in a range of acute and persistent pain conditions, and evidence as treatment of fibromyalgia is considered. Activation of Kv7 potassium channels and agonism at gamma-aminobutyric acid receptor A leading to indirect N-methyl-D-aspartate receptor antagonism is responsible for the analgesic effects of flupirtine and appears to be involved in other symptoms associated with fibromyalgia. Patients with fibromyalgia reported improved control of their symptoms without significant adverse effects in an observational audit in clinical practice. This article presents evidence that flupirtine, or related drugs, is a therapeutic option for the treatment of fibromyalgia. The pharmacology of flupirtine and mechanisms of action involved provide a spectrum of effects that would not only control the chronic pain characteristic of fibromyalgia but many of the other symptoms. Thus, further investigation of the efficacy of flupirtine or related drugs exhibiting a similar pharmacology as a treatment of fibromyalgia would be of interest. oxidase enzymes to the active N-acetylated analogue D13223 and 4-fluorohippuric, which are further oxidised and then conjugated inactive metabolites.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44982045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-01DOI: 10.14218/JERP.2020.00025
H. Rahmoune, N. Boutrid
permits noncommercial unrestricted use, distribution, and reproduction in any medium, provided that the following statement is provided. “This article has been published in Journal of Exploratory Research in Pharmacology at https://doi.org/10.14218/JERP.2020.00025 and can also be viewed on the Journal’s website at https://www.xiahepublishing.com/journal/jerp ”. Journal of Exploratory Research in Pharmacology 2021 vol. 000(000) | 000-000 Epub DOI: 10.14218/JERP.2020.00025
{"title":"Quercetin: the Ultimate Anti-inflammatory Elixir?","authors":"H. Rahmoune, N. Boutrid","doi":"10.14218/JERP.2020.00025","DOIUrl":"https://doi.org/10.14218/JERP.2020.00025","url":null,"abstract":"permits noncommercial unrestricted use, distribution, and reproduction in any medium, provided that the following statement is provided. “This article has been published in Journal of Exploratory Research in Pharmacology at https://doi.org/10.14218/JERP.2020.00025 and can also be viewed on the Journal’s website at https://www.xiahepublishing.com/journal/jerp ”. Journal of Exploratory Research in Pharmacology 2021 vol. 000(000) | 000-000 Epub DOI: 10.14218/JERP.2020.00025","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46496560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01Epub Date: 2020-11-06DOI: 10.14218/jerp.2020.00020
J Ruth Wu-Wong, Jerry L Wessale, Yung-Wu Chen, Theresa Chen, Maysaa Oubaidin, Phimon Atsawasuwan
Background and objectives: VS-105, a novel vitamin D receptor agonist with significantly less hypercalcemic side effects than calcitriol, is a useful tool to investigate whether or not a vitamin D receptor agonist at non-hypercalcemic doses could improve bone mineral density (BMD).
Methods: VS-105 and calcitriol were evaluated in an ovariectomized (OVX) osteoporosis rat model and in calvariae bone organ culture.
Results: Treatment of OVX rats by VS-105 (0.1, 0.2 or 0.5 μg/kg, intraperitoneal, 3×/week, for 90 days) significantly improved BMD in the L3 lumbar vertebra in a dose-dependent manner (sham vs. OVX/vehicle: 324 ± 14 vs. 279 ± 10 mg/cm2; VS-105 at 0.1, 0.2 and 0.5 μg/kg: 306 ± 9, 329 ± 12, and 327 ± 10 mg/cm2, respectively) without affecting serum calcium (Ca). Calcitriol at 0.1 μg/kg significantly increased BMD but it also increased serum Ca. VS-105 and calcitriol at the test doses significantly suppressed serum parathyroid hormone and promoted tibia bone growth. With respect to biomarkers of bone remodeling, calcitriol and VS-105 both significantly elevated serum osteocalcin. In the calvariae bone organ culture, net Ca release was significantly less in VS-105-treated groups (vs. calcitriol).
Conclusions: VS-105 is efficacious in improving BMD in a dose range that does not affect serum Ca in OVX rats; the improvement in BMD by VS-105 is attributable to increased osteoblastic activity and reduced osteoclastic bone resorption.
背景和目的:VS-105是一种新型维生素D受体激动剂，其高钙血症副作用明显小于骨化三醇，是研究非高钙血症剂量维生素D受体激动剂是否能改善骨密度(BMD)的有用工具。方法:在去卵巢骨质疏松大鼠模型和颅骨骨器官培养中评价VS-105和骨化三醇的作用。结果:OVX大鼠经VS-105(0.1、0.2或0.5 μg/kg，腹腔注射，3次/周，持续90天)治疗后，L3腰椎骨密度呈剂量依赖性显著改善(假手术vs. OVX/对照:324±14 vs. 279±10 mg/cm2;VS-105在0.1、0.2和0.5 μg/kg时分别为:306±9、329±12和327±10 mg/cm2)，不影响血清钙(Ca)。0.1 μg/kg骨化三醇可显著提高骨密度，提高血清钙、VS-105含量;骨化三醇可显著抑制血清甲状旁腺激素分泌，促进胫骨生长。骨重塑生物标志物方面，骨化三醇和VS-105均显著升高血清骨钙素。在颅骨骨器官培养中，vs -105处理组的净钙释放量明显低于骨化三醇组。结论:VS-105在不影响血清钙的剂量范围内可有效改善OVX大鼠的骨密度;VS-105对骨密度的改善是由于成骨细胞活性的增加和破骨细胞骨吸收的减少。
{"title":"A Novel Vitamin D Receptor Agonist, VS-105, Improves Bone Mineral Density without Affecting Serum Calcium in a Postmenopausal Osteoporosis Rat Model.","authors":"J Ruth Wu-Wong, Jerry L Wessale, Yung-Wu Chen, Theresa Chen, Maysaa Oubaidin, Phimon Atsawasuwan","doi":"10.14218/jerp.2020.00020","DOIUrl":"https://doi.org/10.14218/jerp.2020.00020","url":null,"abstract":"<p><strong>Background and objectives: </strong>VS-105, a novel vitamin D receptor agonist with significantly less hypercalcemic side effects than calcitriol, is a useful tool to investigate whether or not a vitamin D receptor agonist at non-hypercalcemic doses could improve bone mineral density (BMD).</p><p><strong>Methods: </strong>VS-105 and calcitriol were evaluated in an ovariectomized (OVX) osteoporosis rat model and in calvariae bone organ culture.</p><p><strong>Results: </strong>Treatment of OVX rats by VS-105 (0.1, 0.2 or 0.5 μg/kg, intraperitoneal, 3×/week, for 90 days) significantly improved BMD in the L3 lumbar vertebra in a dose-dependent manner (sham vs. OVX/vehicle: 324 ± 14 vs. 279 ± 10 mg/cm<sup>2</sup>; VS-105 at 0.1, 0.2 and 0.5 μg/kg: 306 ± 9, 329 ± 12, and 327 ± 10 mg/cm<sup>2</sup>, respectively) without affecting serum calcium (Ca). Calcitriol at 0.1 μg/kg significantly increased BMD but it also increased serum Ca. VS-105 and calcitriol at the test doses significantly suppressed serum parathyroid hormone and promoted tibia bone growth. With respect to biomarkers of bone remodeling, calcitriol and VS-105 both significantly elevated serum osteocalcin. In the calvariae bone organ culture, net Ca release was significantly less in VS-105-treated groups (vs. calcitriol).</p><p><strong>Conclusions: </strong>VS-105 is efficacious in improving BMD in a dose range that does not affect serum Ca in OVX rats; the improvement in BMD by VS-105 is attributable to increased osteoblastic activity and reduced osteoclastic bone resorption.</p>","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":"5 4","pages":"73-80"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/6a/nihms-1646874.PMC8478347.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39471116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-30DOI: 10.14218/jerp.2019.00007
J. Adesanwo, I. Ajayi, O. Ajayi, O. Igbeneghu, A. McDonald
The chemical composition of Melanthera scandens (MS) methanol (MeOH) extract is yet to be fully comprehended. Chemical composition of a plant extract is closely related to the biological activity of the plant material, in phytomedicine. In this study, chemical analyses of MS extracts were carried out with the aim of identifying the organic chemical constituents.
{"title":"Identification of Chemical Constituents and Evaluation of the Antibacterial Activity of Methanol Extract and Fractions of the Leaf of Melanthera scandens (Schum. et Thonn.) Roberty","authors":"J. Adesanwo, I. Ajayi, O. Ajayi, O. Igbeneghu, A. McDonald","doi":"10.14218/jerp.2019.00007","DOIUrl":"https://doi.org/10.14218/jerp.2019.00007","url":null,"abstract":"The chemical composition of Melanthera scandens (MS) methanol (MeOH) extract is yet to be fully comprehended. Chemical composition of a plant extract is closely related to the biological activity of the plant material, in phytomedicine. In this study, chemical analyses of MS extracts were carried out with the aim of identifying the organic chemical constituents.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49020277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-21DOI: 10.14218/JERP.2019.00001
S. Gurunath, Arun Koyyada, Amgoth Vamshi Krishna, L. Kavya, B. Sridhar
Thyroid disorder and diabetes are associated endocrine disorders. Patients with either one of the disorders are at great risk of developing the other. The co-existence of type-2 diabetes mellitus (T2DM) and hypothyroidism with clinical evidence of effect on one another has not been reported until today.
{"title":"Clinical Evidence of Association Between Type-2 Diabetes Mellitus and Hypothyroidism with Therapeutic Relevance—An Observational Study","authors":"S. Gurunath, Arun Koyyada, Amgoth Vamshi Krishna, L. Kavya, B. Sridhar","doi":"10.14218/JERP.2019.00001","DOIUrl":"https://doi.org/10.14218/JERP.2019.00001","url":null,"abstract":"Thyroid disorder and diabetes are associated endocrine disorders. Patients with either one of the disorders are at great risk of developing the other. The co-existence of type-2 diabetes mellitus (T2DM) and hypothyroidism with clinical evidence of effect on one another has not been reported until today.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47960621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-30DOI: 10.14218/JERP.2019.00002
H. Rahmoune, N. Boutrid, M. Amrane, B. Bioud
Hepatocellular carcinoma is a devastating malignancy in childhood. We highlight some specific aspects in the pediatric population, especially involving metabolic diseases like tyrosinemia type 1. Pediatric hepatocellular carcinoma is the second most common malignant liver cancer and differs from the adult form in its etiologies, biological behavior, and low frequency of cirrhosis.1,2 The main pediatric causes of hepatocellular carcinoma are hepatitis B virus infection and genetic/metabolic disorders, such as hepatorenal tyrosinemia, familial progressive intrahepatic cholestasis, glycogen storage diseases, and Alagille’s syndrome.2 The age that hepatocellular carcinoma typically affects children is 10–14 years (median), and it is often metastatic or locally advanced at diagnosis. However, due to mass immunization against hepatitis B virus, the epidemiologic and clinical profiles of pediatric hepatocellular carcinoma are shifting; younger patients with congenital and metabolic liver disease now make up the major portion of patients with hepatocellular carcinoma.3 Thus, management of any predisposing liver disease is highly recommended for preventing and detecting hepatocellular carcinoma.2,4 Currently, the most important metabolic disorder leading to hepatocellular carcinoma is tyrosinemia type I (hepatorenal tyrosinemia), an autosomal recessive condition resulting in hepatic failure with renal and neurological comorbidities and long-term risks for hepatic carcinoma.5 In fact, due to the enzyme deficiency (fumarylacetoacetate hydrolase deficiency) in hepatorenal tyrosinemia, the substrate fumarylacetoacetate accumulates. This accumulating fumarylacetoacetate and its precursor, maleylacetoacetate, is mutagenic and causes chromosomal instability, cell cycle arrest, and apoptosis, leading first to liver cirrhosis and later on to hepatocellular carcinoma.6 The molecular basis of the pathogenic liver process in hepatorenal tyrosinemia is still unclear. Multiple signaling pathways involved in cell proliferation, differentiation, and cancer have been found to be rapidly deregulated in hepatorenal tyrosinemia-model mice. The p21 and mTOR pathways, critical regulators of proliferation and tumorigenesis, have also been found to be dysregulated.7 Interestingly, an effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione exists.5–7 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione prevents the development of hepatocellular carcinoma when started early but fails to stop this malignancy if prescribed at a later stage, stressing the importance of a prompt diagnosis and management of hepatorenal tyrosinemia.8 Prior to the availability of 2-[2-nitro4-trifluoromethylbenzoyl]-1,3-cyclohexanedione for the treatment of hepatorenal tyrosinemia, the only definitive therapy of liver damage was transplantation. Nowadays, hepatic grafting is reserved for hepatorenal tyrosinemia pediatric cases with severe liver failure who fail to r
{"title":"Pediatric Hepatocellular Carcinoma: Metabolic Causes and Possible Prevention","authors":"H. Rahmoune, N. Boutrid, M. Amrane, B. Bioud","doi":"10.14218/JERP.2019.00002","DOIUrl":"https://doi.org/10.14218/JERP.2019.00002","url":null,"abstract":"Hepatocellular carcinoma is a devastating malignancy in childhood. We highlight some specific aspects in the pediatric population, especially involving metabolic diseases like tyrosinemia type 1. Pediatric hepatocellular carcinoma is the second most common malignant liver cancer and differs from the adult form in its etiologies, biological behavior, and low frequency of cirrhosis.1,2 The main pediatric causes of hepatocellular carcinoma are hepatitis B virus infection and genetic/metabolic disorders, such as hepatorenal tyrosinemia, familial progressive intrahepatic cholestasis, glycogen storage diseases, and Alagille’s syndrome.2 The age that hepatocellular carcinoma typically affects children is 10–14 years (median), and it is often metastatic or locally advanced at diagnosis. However, due to mass immunization against hepatitis B virus, the epidemiologic and clinical profiles of pediatric hepatocellular carcinoma are shifting; younger patients with congenital and metabolic liver disease now make up the major portion of patients with hepatocellular carcinoma.3 Thus, management of any predisposing liver disease is highly recommended for preventing and detecting hepatocellular carcinoma.2,4 Currently, the most important metabolic disorder leading to hepatocellular carcinoma is tyrosinemia type I (hepatorenal tyrosinemia), an autosomal recessive condition resulting in hepatic failure with renal and neurological comorbidities and long-term risks for hepatic carcinoma.5 In fact, due to the enzyme deficiency (fumarylacetoacetate hydrolase deficiency) in hepatorenal tyrosinemia, the substrate fumarylacetoacetate accumulates. This accumulating fumarylacetoacetate and its precursor, maleylacetoacetate, is mutagenic and causes chromosomal instability, cell cycle arrest, and apoptosis, leading first to liver cirrhosis and later on to hepatocellular carcinoma.6 The molecular basis of the pathogenic liver process in hepatorenal tyrosinemia is still unclear. Multiple signaling pathways involved in cell proliferation, differentiation, and cancer have been found to be rapidly deregulated in hepatorenal tyrosinemia-model mice. The p21 and mTOR pathways, critical regulators of proliferation and tumorigenesis, have also been found to be dysregulated.7 Interestingly, an effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione exists.5–7 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione prevents the development of hepatocellular carcinoma when started early but fails to stop this malignancy if prescribed at a later stage, stressing the importance of a prompt diagnosis and management of hepatorenal tyrosinemia.8 Prior to the availability of 2-[2-nitro4-trifluoromethylbenzoyl]-1,3-cyclohexanedione for the treatment of hepatorenal tyrosinemia, the only definitive therapy of liver damage was transplantation. Nowadays, hepatic grafting is reserved for hepatorenal tyrosinemia pediatric cases with severe liver failure who fail to r","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44198919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-30DOI: 10.14218/JERP.2019.00003
Xiao-Ya Yang, Yuan-Yuan Zhang, W. Xie, S. H. He, Li-Hao Wu, Xingxiang He, H. Xia
Hepatitis C virus (HCV) infects at least 150 million people chronically worldwide. It is a major risk factor for cirrhosis, hepatocellular carcinoma, and death. Direct-acting antiviral therapy is very efficacious in treating HCV infection but it is inaccessible and unavailable in some developing countries. Therefore, searching for more effective and easily accessible regimens remains an urgent need. The aim of this article is to review the anti-HCV effects of herbal medicines from experimental to clinical evidence, and discuss current issues, hurdles and future perspectives for their application from bench to bedside. Numerous in vitro studies have indicated that many herbs work effectively in exerting anti-HCV activities. Yet, only a few animal experiments have been conducted that demonstrate the anti-HCV effects of these medicines; in addition, these results do not show an ability to eliminate the virus completely from the infected animals. Thus far, clinical trials have produced inconclusive anti-HCV results in terms of efficacy and safety, presumably due to the lack of the quality of methodologies used in the trials. In conclusion, despite apparent anti-HCV activities in vitro, clinical efficacy and safety of herbal medicines for the treatment of HCV infection have not been revealed convincingly. More animal studies using ideal models and more well-designed clinical trials with a larger sample sizes and longer treatment periods, taking the body habitus into consideration, are required to further assess the efficacy and safety of herbal medicines for HCV infection.
{"title":"Herbal Medicines for Hepatitis C Virus Infection: The Exploratory Journey from Bench to Bedside Still Has a Long Way to Go","authors":"Xiao-Ya Yang, Yuan-Yuan Zhang, W. Xie, S. H. He, Li-Hao Wu, Xingxiang He, H. Xia","doi":"10.14218/JERP.2019.00003","DOIUrl":"https://doi.org/10.14218/JERP.2019.00003","url":null,"abstract":"Hepatitis C virus (HCV) infects at least 150 million people chronically worldwide. It is a major risk factor for cirrhosis, hepatocellular carcinoma, and death. Direct-acting antiviral therapy is very efficacious in treating HCV infection but it is inaccessible and unavailable in some developing countries. Therefore, searching for more effective and easily accessible regimens remains an urgent need. The aim of this article is to review the anti-HCV effects of herbal medicines from experimental to clinical evidence, and discuss current issues, hurdles and future perspectives for their application from bench to bedside. Numerous in vitro studies have indicated that many herbs work effectively in exerting anti-HCV activities. Yet, only a few animal experiments have been conducted that demonstrate the anti-HCV effects of these medicines; in addition, these results do not show an ability to eliminate the virus completely from the infected animals. Thus far, clinical trials have produced inconclusive anti-HCV results in terms of efficacy and safety, presumably due to the lack of the quality of methodologies used in the trials. In conclusion, despite apparent anti-HCV activities in vitro, clinical efficacy and safety of herbal medicines for the treatment of HCV infection have not been revealed convincingly. More animal studies using ideal models and more well-designed clinical trials with a larger sample sizes and longer treatment periods, taking the body habitus into consideration, are required to further assess the efficacy and safety of herbal medicines for HCV infection.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46389332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-28DOI: 10.14218/JERP.2018.00013
J. Adesanwo, Clifford O. Egbomeade, D. Moronkola, D. Akinpelu
Compositae species are applied as whole or part of the feed stock for animals and poultry. However, rabbits display varied preferences in their consumption of these plants, following the order of: Melanthera scandens (MS) > Synedrella nodiflora (SN) > Aspilia africana (AA) > Ageratum conyzoides (AC). This preference profile may be due to variation in chemical composition, flavor or toxicity of the plants. The rabbits in our farm feed on 100% MS or SN with excellent performance. This study, therefore, is set to: obtain the methanol extract of these plants, screen them for their antibacterial activity, determine their toxicity and investigate the chemical composition of their n-hexane fraction (volatile constituents).
{"title":"Chemical, Toxicity and Antibacterial Studies on Methanol Extracts of Melanthera scandens, Ageratum conyzoides, Aspilia africana and Syndrella nodiflora","authors":"J. Adesanwo, Clifford O. Egbomeade, D. Moronkola, D. Akinpelu","doi":"10.14218/JERP.2018.00013","DOIUrl":"https://doi.org/10.14218/JERP.2018.00013","url":null,"abstract":"Compositae species are applied as whole or part of the feed stock for animals and poultry. However, rabbits display varied preferences in their consumption of these plants, following the order of: Melanthera scandens (MS) > Synedrella nodiflora (SN) > Aspilia africana (AA) > Ageratum conyzoides (AC). This preference profile may be due to variation in chemical composition, flavor or toxicity of the plants. The rabbits in our farm feed on 100% MS or SN with excellent performance. This study, therefore, is set to: obtain the methanol extract of these plants, screen them for their antibacterial activity, determine their toxicity and investigate the chemical composition of their n-hexane fraction (volatile constituents).","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48449222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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