Evaluation of antibacterial activity of vitamin C against human bacterial pathogens / Avaliação da atividade antibacteriana da vitamina C contra patógenos bacterianos humanos

Now a day’s multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans.

Agora, a resistência antimicrobiana de um dia em patógenos aos antibióticos tornou-se a principal causa de preocupação e houve uma realização inadequada no desenvolvimento de novos antibióticos para tratar infecções bacterianas. Portanto, há uma necessidade de pesquisar um novo adjuvante, e a vitamina C é um desses adjuvantes promissores. O objetivo do presente estudo foi elucidar o efeito antibacteriano da vitamina C em diferentes temperaturas (4 °C, 37 °C e 50 °C) e pH (3, 8 e 11), contra Gram-positivos e Gram-cepas bacterianas negativas em várias concentrações (5-20 mg / ml) através do método de difusão em ágar bem. A inibição do crescimento de todas as cepas bacterianas pela vitamina C era dependente da concentração. A vitamina C inibiu significativamente o crescimento de bactérias Gram-positivas: Bacillus licheniformis (25,3 ± 0,9 mm), Staphylococcus aureus (22,0 ± 0,6 mm), Bacillus subtilis (19,3 ± 0,3 mm) e bactérias Gram- negativas: Proteus mirabilis (27,7 ± 0,9 mm), Klebsiella pneumoniae (21,3 ± 0,9 mm), Pseudomonas aeruginosa (18,0 ± 1,5 mm) e Escherichia coli (18,3 ± 0,3 mm). A estabilidade da vitamina C foi observada em vários valores de pH e várias temperaturas. A vitamina C mostrou atividade antibacteriana significativa em pH ácido contra todas as cepas bacterianas. A estabilidade da vitamina C permaneceu nas mesmas diferentes temperaturas (4 °C, 37 °C e 50 °C). Concluímos que a vitamina C é um agente antibacteriano eficaz e seguro que pode ser usado no futuro como uma opção de tratamento auxiliar para combater infecções em humanos, pois pode apoiar o sistema imunológico diretamente.

Evaluation of antibacterial activity of vitamin C against human bacterial pathogens

Abstract Now a days multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans.

Resumo Agora, a resistência antimicrobiana de um dia em patógenos aos antibióticos tornou-se a principal causa de preocupação e houve uma realização inadequada no desenvolvimento de novos antibióticos para tratar infecções bacterianas. Portanto, há uma necessidade de pesquisar um novo adjuvante, e a vitamina C é um desses adjuvantes promissores. O objetivo do presente estudo foi elucidar o efeito antibacteriano da vitamina C em diferentes temperaturas (4 °C, 37 °C e 50 °C) e pH (3, 8 e 11), contra Gram-positivos e Gram-cepas bacterianas negativas em várias concentrações (5-20 mg / ml) através do método de difusão em ágar bem. A inibição do crescimento de todas as cepas bacterianas pela vitamina C era dependente da concentração. A vitamina C inibiu significativamente o crescimento de bactérias Gram-positivas: Bacillus licheniformis (25,3 ± 0,9 mm), Staphylococcus aureus (22,0 ± 0,6 mm), Bacillus subtilis (19,3 ± 0,3 mm) e bactérias Gram- negativas: Proteus mirabilis (27,7 ± 0,9 mm), Klebsiella pneumoniae (21,3 ± 0,9 mm), Pseudomonas aeruginosa (18,0 ± 1,5 mm) e Escherichia coli (18,3 ± 0,3 mm). A estabilidade da vitamina C foi observada em vários valores de pH e várias temperaturas. A vitamina C mostrou atividade antibacteriana significativa em pH ácido contra todas as cepas bacterianas. A estabilidade da vitamina C permaneceu nas mesmas diferentes temperaturas (4 °C, 37 °C e 50 °C). Concluímos que a vitamina C é um agente antibacteriano eficaz e seguro que pode ser usado no futuro como uma opção de tratamento auxiliar para combater infecções em humanos, pois pode apoiar o sistema imunológico diretamente.

Phytochemical screening, antimicrobial activity, in vitro and in vivo antioxidant activity of Berberis lycium Royle root bark extract.

Antioxidants are materials that scavenge or remove free radicals from living systems. The oxidation process ends in the production of free radicals. These free radicals are the chief birthplace of cancerous cells. Antioxidizing agents remove free radical intermediates by terminating oxidation processes by being oxidized themselves. On the other hand, infectious diseases affect the world on a large scale. To fight these diseases several synthetic compounds have been used. Plant based medications play important role in this regard. So, the current research aimed to investigate the antibacterial and antioxidant effect of Berberis lycium Royle root bark (BLR) extract. Berberis lycium Royle was used for phytochemical analysis and also as antimicrobial and antioxidant agents. The antimicrobial activity was evaluated by the agar well diffusion method. Current study revealed that BLR was rich in phytochemicals and toxic against tested pathogenic bacteria. BLR showed the highest activity against S. pyogenes (13.3±0.8 mm). The lowest antibacterial activity was reported against E. coli (0±0 mm). In case of minimum inhibitory concentration, it was observed that BLR with 10 µg/mL concentration showed the highest activity while 2.5 µg/mL of BLR showed the least inhibitory activity. The highest In vitro antioxidant activity was recorded as 65% at 100 µg/mL. In case of in vivo antioxidant activity level of CAT, GSH and SOD were decreased while that of MDA was enhanced in groups treated with CCl4 as compared to the control group. BLR extract treatment reversed all these changes significantly. Current results indicate that BLR is effective against bacterial pathogens and also has antioxidant potential.

Evaluation of antibacterial activity of vitamin C against human bacterial pathogens.

Now a day's multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice / Avaliação dos efeitos quimiopreventivo e quimioterápico do extrato de Artemisia vulgaris contra carcinogênese hepatocelular induzida por dietilnitrosamina em camundongos Balb C

The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice / Avaliação dos efeitos quimiopreventivo e quimioterápico do extrato de Artemisia vulgaris contra carcinogênese hepatocelular induzida por dietilnitrosamina em camundongos Balb C

Abstract The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

Resumo O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 μl/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5' nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice.

The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 µl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 µl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 µl/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

In vivo induction of hepatocellular carcinoma by diethylnitrosoamine and pharmacological intervention in Balb C mice using Bergenia ciliata extracts / Indução in vivo de carcinoma hepatocelular por dietilnitrosoamina e intervenção farmacológica em camundongos balb c usando extratos de Bergenia ciliata

Abstract Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 μg/μl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.

Resumo Antecedentes O carcinoma hepatocelular é a neoplasia primária mais frequente do fígado e é responsável por até um milhão de mortes em todo o mundo em um ano. Objetivos O objetivo do presente estudo foi avaliar a eficiência anticancerígena do rizoma de Bergenia ciliata contra a hepatocarcinogênese induzida por dietilnitrosoamina em camundongos balb c. Métodos Um por cento de dietilnitrosoamina foi preparado usando 99 ml de solução salina normal (0,9 por cento) à qual foi adicionado 1 ml de solução concentrada de dietilnitrosoamina (DEN) (0,01 μg / μl). O extrato de Bergenia ciliata foi preparado pela técnica de maceração. Os ratos foram classificados em quatro grupos: Grupo 1 grupo controle (N = 7) recebeu solução salina (3,5 mL / mg), grupo 2 (N = 14) recebeu dietilnitrosoamina (3,5 mL / mg) por via intraperitoneal uma vez por semana para oito semanas consecutivas, o grupo 3 (N = 7) recebeu extrato vegetal (150 mg / kg (peso corporal)) uma vez por semana, enquanto o grupo 4 (N = 7) recebeu combinação de dietilnitrosoamina (3,5 μl / mg) e extrato (150 mg / kg (peso corporal). Após oito semanas do grupo de indução DEN 2 ratos foram divididos em dois subgrupos contendo sete ratos cada, subgrupo 1 foi sacrificado enquanto subgrupo 2 foi tratado com extrato vegetal (150 mg / kg)) uma vez por semana durante oito semanas consecutivas. Resultados O modelo de camundongos hepatocelulares carcinômicos (CHC) injetados com DEN provocou declínio significativo nos níveis de albumina com elevações significativas concomitantes nos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato ehidrogenase (G6PDH) e bilirrubina. A administração intraperitoneal de B. ciliata como agente protetor produziu um aumento significativo nos níveis de albumina com uma diminuição significativa nos níveis dos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato desidrogenase (G6PDH) e bilirrubina. Conclusão Bergenia ciliata possui atividade antioxidante potente, capacidade de eliminação de radicais livres e propriedades anticancerígenas. Extratos de Bergenia ciliata podem fornecer uma base para o desenvolvimento de drogas anti-cancerígenas.

In vivo induction of hepatocellular carcinoma by diethylnitrosoamine and pharmacological intervention in Balb C mice using Bergenia ciliata extracts.

BACKGROUND: Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. OBJECTIVES: The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. METHODS: One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 µg/µl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 µl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 µl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 µl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. RESULTS: The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. CONCLUSION: Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker.

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

In vivo induction of hepatocellular carcinoma by diethylnitrosoamine and pharmacological intervention in Balb C mice using Bergenia ciliata extracts

Abstract Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 g/l). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 l/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.

Resumo Antecedentes O carcinoma hepatocelular é a neoplasia primária mais frequente do fígado e é responsável por até um milhão de mortes em todo o mundo em um ano. Objetivos O objetivo do presente estudo foi avaliar a eficiência anticancerígena do rizoma de Bergenia ciliata contra a hepatocarcinogênese induzida por dietilnitrosoamina em camundongos balb c. Métodos Um por cento de dietilnitrosoamina foi preparado usando 99 ml de solução salina normal (0,9 por cento) à qual foi adicionado 1 ml de solução concentrada de dietilnitrosoamina (DEN) (0,01 g / l). O extrato de Bergenia ciliata foi preparado pela técnica de maceração. Os ratos foram classificados em quatro grupos: Grupo 1 grupo controle (N = 7) recebeu solução salina (3,5 mL / mg), grupo 2 (N = 14) recebeu dietilnitrosoamina (3,5 mL / mg) por via intraperitoneal uma vez por semana para oito semanas consecutivas, o grupo 3 (N = 7) recebeu extrato vegetal (150 mg / kg (peso corporal)) uma vez por semana, enquanto o grupo 4 (N = 7) recebeu combinação de dietilnitrosoamina (3,5 l / mg) e extrato (150 mg / kg (peso corporal). Após oito semanas do grupo de indução DEN 2 ratos foram divididos em dois subgrupos contendo sete ratos cada, subgrupo 1 foi sacrificado enquanto subgrupo 2 foi tratado com extrato vegetal (150 mg / kg)) uma vez por semana durante oito semanas consecutivas. Resultados O modelo de camundongos hepatocelulares carcinômicos (CHC) injetados com DEN provocou declínio significativo nos níveis de albumina com elevações significativas concomitantes nos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato ehidrogenase (G6PDH) e bilirrubina. A administração intraperitoneal de B. ciliata como agente protetor produziu um aumento significativo nos níveis de albumina com uma diminuição significativa nos níveis dos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato desidrogenase (G6PDH) e bilirrubina. Conclusão Bergenia ciliata possui atividade antioxidante potente, capacidade de eliminação de radicais livres e propriedades anticancerígenas. Extratos de Bergenia ciliata podem fornecer uma base para o desenvolvimento de drogas anti-cancerígenas.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice

Abstract The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

Resumo O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.

Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal disorders involving hematopoietic stem and progenitor cells and are associated with myeloproliferation, splenomegaly and constitutional symptoms. Similar signs and symptoms can also be found in patients with chronic inflammatory diseases, and inflammatory processes have been found to play an important role in the pathogenesis and progression of MPNs. Signal transduction pathways involving JAK1, JAK2, STAT3 and STAT5 are causally involved in driving both the malignant cells and the inflammatory process. Moreover, anti-inflammatory and immune-modulating drugs have been used successfully in the treatment of MPNs. However, to date, many unresoved issues remain. These include the role of somatic mutations that are present in addition to JAK2V617F, CALR and MPL W515 mutations, the interdependency of malignant and nonmalignant cells and the means to eradicate MPN-initiating and -maintaining cells. It is imperative for successful therapeutic approaches to define whether the malignant clone or the inflammatory cells or both should be targeted. The present review will cover three aspects of the role of inflammation in MPNs: inflammatory states as important differential diagnoses in cases of suspected MPN (that is, in the absence of a clonal marker), the role of inflammation in MPN pathogenesis and progression and the use of anti-inflammatory drugs for MPNs. The findings emphasize the need to separate the inflammatory processes from the malignancy in order to improve our understanding of the pathogenesis, diagnosis and treatment of patients with Philadelphia-negative MPNs.

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

At present, allo-SCT is the only curative treatment for patients with myelofibrosis (MF). Unfortunately, a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at the time of diagnosis. The approval of the first JAK inhibitor, ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support for assessing the drug's candidacy in the peritransplant period. The drug's precise impact on clinical outcome following allo-SCT is currently not known; nor are the drug's long-term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who undergo allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology Annual Meeting in New Orleans, USA on 6 December 2013, and the European Hematology Association's Annual Meeting in Milan, Italy on 13 June 2014. This document summarizes the results of these efforts.

Biology and clinical management of myeloproliferative neoplasms and development of the JAK inhibitor ruxolitinib.

Myeloproliferative neoplasms (MPN) are debilitating stem cell-derived clonal myeloid malignancies. Conventional treatments for the BCR-ABL1-negative MPN including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) have, so far, been unsatisfactory. Following the discovery of dysregulated JAK-STAT signaling in patients with MPN, many efforts have been directed toward the development of molecularly targeted therapies, including inhibitors of JAK1 and JAK2. Ruxolitinib (previously known as INCB018424; Incyte Corporation, Wilmington, Delaware, USA) is a rationally designed potent oral JAK1 and JAK2 inhibitor that has undergone clinical trials in patients with PV, ET, and PMF. Ruxolitinib was approved on November 16, 2011 by the United States Food and Drug Administration for the treatment of intermediate or high-risk myelofibrosis (MF), including patients with PMF, post-PV MF, and post-ET MF. In randomized phase III studies, ruxolitinib treatment resulted in significant and durable reductions in splenomegaly and improvements in disease-related symptoms in patients with MF compared with placebo or best available therapy. The most common adverse events were anemia and thrombocytopenia, which were manageable and rarely led to discontinuation. This review addresses the cellular and molecular biology, and the clinical management of MPN.

Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium.

Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7-8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new 'Dynamic International Prognostic Scoring System (DIPSS)-plus' prognostic model for primary myelofibrosis (PMF) and the clinical relevance of distinguishing essential thrombocythemia from prefibrotic PMF are discussed.

Chronic myeloproliferative diseases with and without the Ph chromosome: some unresolved issues.

Ph-positive chronic myeloid leukemia (CML) and Ph-negative chronic myeloproliferative diseases (MPDs), characterized in many cases by the presence of the JAK2(V617F) mutation, have many features in common and yet also show fundamental differences. In this review, we pose five discrete and related questions relevant to both categories of hematological malignancy, namely: What are the mechanisms that underlie disease progression from a relatively benign or chronic phase? By what therapeutic methods might one target residual leukemia stem cells in CML? Is JAK2(V617F) the original molecular event in MPD? What epigenetic events must have a role in dictating disease phenotype in MPDs? And finally, Will the benefits conferred by current or future JAK2(V617F) inhibitors equal or even surpass the clinical success that has resulted from the use of tyrosine kinase inhibitors in CML? These and others questions must be addressed and in some cases should be answered in the foreseeable future.