Overall survival of high-risk neuroblastoma patients is still poor, emphasizing the need for novel therapeutic options. There is evidence for anti-cancer properties of the herbal substances thymoquinone and curcumin. These substances are isolated from Nigella sativa L. and Curcuma longa L., respectively, which are used in traditional medicine.
We investigated cytotoxic effects of thymoquinone and curcumin on neuroblastoma cell lines NLF, NB69, and SK-N-BE(2), in vitro.
Cytotoxicity of compounds was investigated by MTT cell viability assays. For analyzing effects on cell proliferation BrdU assays were employed and induction of apoptosis was detected by Cell Death ELISA assays.
Both substances showed cytotoxic effects in all three neuroblastoma cell lines, whereby primary human fibroblast cells reacted less sensitively. Overall, lower IC50 values could be calculated for curcumin (3.75-7.42 µM) than for thymoquinone (5.16-16.3 µM). https://www.selleckchem.com/products/genipin.html Decreased proliferation and increased apoptosis rates were observed under treatment.
Both substances showed anti-tumoral properties on neuroblastoma cell lines and should be further investigated as therapeutic agents.
Both substances showed anti-tumoral properties on neuroblastoma cell lines and should be further investigated as therapeutic agents.
Wolfram syndrome is a rare neurodegenerative disorder, characterized by the presence of diabetes insipidus, diabetes mellitus, optic atrophy, and sensorineural deafness. The majority of cases are due to autosomal recessive biallelic variants in the WFS1 gene; however, pathogenic autosomal dominant (AD) mutations have also been described. Glucagon-like peptide (GLP-1) agonists have been studied in both animal models and humans with classic Wolfram syndrome.
We present a 15-year-old female with a personal and family history of congenital strabismus, bilateral cataracts, low-frequency sensorineural hearing loss, and diabetes mellitus. Trio whole exome sequencing revealed a previously unknown maternally inherited heterozygous variant in exon 8 of the WFS1 gene c.2605_2616del12 p.Ser869_His872del, leading to the diagnosis of AD WFS1-related disorder. Treatment with a GLP-1 agonist resulted in marked improvement in glycemic control and discontinuation of insulin therapy. This patient's response to a GLP-1 agonist provides suggestive indirect evidence for a role of WFS1 on β-cell endoplasmic reticulum stress and suggests that treatment with a GLP-1 agonist should be considered in patients with dominant forms of WS.
We present a 15-year-old female with a personal and family history of congenital strabismus, bilateral cataracts, low-frequency sensorineural hearing loss, and diabetes mellitus. Trio whole exome sequencing revealed a previously unknown maternally inherited heterozygous variant in exon 8 of the WFS1 gene c.2605_2616del12 p.Ser869_His872del, leading to the diagnosis of AD WFS1-related disorder. Treatment with a GLP-1 agonist resulted in marked improvement in glycemic control and discontinuation of insulin therapy. This patient's response to a GLP-1 agonist provides suggestive indirect evidence for a role of WFS1 on β-cell endoplasmic reticulum stress and suggests that treatment with a GLP-1 agonist should be considered in patients with dominant forms of WS.
Mucopolysaccharidosis type II (MPS-II) or Hunter syndrome is a rare X-linked recessive disorder caused by genetic lesions in the IDS gene, encoding the iduronate-2-sulfatase (IDS) enzyme, disrupting the metabolism of certain sulfate components of the extracellular matrix. Thus, the undegraded components, also known as glycosaminoglycans, accumulate in multiple tissues resulting in multisystemic abnormalities.
To uncover causative genetic lesions in probands of three unrelated Pakistani families affected with rare X-linked recessive Hunter syndrome.
Screening of the IDS gene was performed in six individuals (three patients and their mothers) through whole genomic DNA extraction from peripheral blood followed by PCR and Sanger sequencing. MutationTaster, PROVEAN, Human Splicing Finder, Swiss-Model, and SwissPdbViewer were used for in silico analysis of identified variants.
All probands were presented with coarse facies, recurrent respiratory tract infection, and reduced IDS activity. Molecular screeningesult of nonsense-mediated mRNA decay. Our study provides the first genetic depiction of MPS-II in Pakistan, expands the global IDS mutation spectrum, may provide insights into the three-dimensional structure of IDS, and should benefit the affected families in genetic counseling and prenatal diagnosis.
The interaction of diet with gut microbiome has been implicated in the onset of cardiovascular disease. The gut microbiome displays diurnal rhythms, which may be influenced by meal timing.
This study aimed to investigate the effect of the timing of main meal consumption on the microbiome and cardiometabolic biomarkers of the host.
Seventeen healthy adults randomly consumed an isocaloric diet for 7 days, twice, by alternating lunch with dinner meals, and with a 2-week washout in-between. Sixty percent of the participants' daily energy requirements was consumed either as lunch or dinner, respectively. Meals were provided free to the participants. All fecal samples produced the last 3 days of each intervention were collected and analyzed for microbial profiling (16S rRNA gene amplicon sequencing), quantitative estimation of representative bacterial groups (qPCR) of the gut microbiome, and the output of short-chain fatty acids (SCFA) in feces. Fasted blood samples were analyzed for low-grade inflammatory biomarkers, blood lipids, insulin, and glucose levels. Cumulative energy loss in feces was measured over the collection period using bomb calorimetry.
Meal timing had no significant effects on fecal SCFA output, energy loss in feces, microbial community profiling, and bacterial species relative abundance. The absolute concentration of Escherichia coli was significantly higher after the large lunch intervention (p = 0.02). No effects on blood biomarkers of cardiometabolic health were observed.
In a well-controlled study, main meal timing displayed minimal acute effects on the gut microbiome composition, its diet-related function, and blood biomarkers of cardiometabolic health.
In a well-controlled study, main meal timing displayed minimal acute effects on the gut microbiome composition, its diet-related function, and blood biomarkers of cardiometabolic health.
Overall survival of high-risk neuroblastoma patients is still poor, emphasizing the need for novel therapeutic options. There is evidence for anti-cancer properties of the herbal substances thymoquinone and curcumin. These substances are isolated from Nigella sativa L. and Curcuma longa L., respectively, which are used in traditional medicine.
We investigated cytotoxic effects of thymoquinone and curcumin on neuroblastoma cell lines NLF, NB69, and SK-N-BE(2), in vitro.
Cytotoxicity of compounds was investigated by MTT cell viability assays. For analyzing effects on cell proliferation BrdU assays were employed and induction of apoptosis was detected by Cell Death ELISA assays.
Both substances showed cytotoxic effects in all three neuroblastoma cell lines, whereby primary human fibroblast cells reacted less sensitively. Overall, lower IC50 values could be calculated for curcumin (3.75-7.42 µM) than for thymoquinone (5.16-16.3 µM). https://www.selleckchem.com/products/genipin.html Decreased proliferation and increased apoptosis rates were observed under treatment.
Both substances showed anti-tumoral properties on neuroblastoma cell lines and should be further investigated as therapeutic agents.
Both substances showed anti-tumoral properties on neuroblastoma cell lines and should be further investigated as therapeutic agents.
Wolfram syndrome is a rare neurodegenerative disorder, characterized by the presence of diabetes insipidus, diabetes mellitus, optic atrophy, and sensorineural deafness. The majority of cases are due to autosomal recessive biallelic variants in the WFS1 gene; however, pathogenic autosomal dominant (AD) mutations have also been described. Glucagon-like peptide (GLP-1) agonists have been studied in both animal models and humans with classic Wolfram syndrome.
We present a 15-year-old female with a personal and family history of congenital strabismus, bilateral cataracts, low-frequency sensorineural hearing loss, and diabetes mellitus. Trio whole exome sequencing revealed a previously unknown maternally inherited heterozygous variant in exon 8 of the WFS1 gene c.2605_2616del12 p.Ser869_His872del, leading to the diagnosis of AD WFS1-related disorder. Treatment with a GLP-1 agonist resulted in marked improvement in glycemic control and discontinuation of insulin therapy. This patient's response to a GLP-1 agonist provides suggestive indirect evidence for a role of WFS1 on β-cell endoplasmic reticulum stress and suggests that treatment with a GLP-1 agonist should be considered in patients with dominant forms of WS.
We present a 15-year-old female with a personal and family history of congenital strabismus, bilateral cataracts, low-frequency sensorineural hearing loss, and diabetes mellitus. Trio whole exome sequencing revealed a previously unknown maternally inherited heterozygous variant in exon 8 of the WFS1 gene c.2605_2616del12 p.Ser869_His872del, leading to the diagnosis of AD WFS1-related disorder. Treatment with a GLP-1 agonist resulted in marked improvement in glycemic control and discontinuation of insulin therapy. This patient's response to a GLP-1 agonist provides suggestive indirect evidence for a role of WFS1 on β-cell endoplasmic reticulum stress and suggests that treatment with a GLP-1 agonist should be considered in patients with dominant forms of WS.
Mucopolysaccharidosis type II (MPS-II) or Hunter syndrome is a rare X-linked recessive disorder caused by genetic lesions in the IDS gene, encoding the iduronate-2-sulfatase (IDS) enzyme, disrupting the metabolism of certain sulfate components of the extracellular matrix. Thus, the undegraded components, also known as glycosaminoglycans, accumulate in multiple tissues resulting in multisystemic abnormalities.
To uncover causative genetic lesions in probands of three unrelated Pakistani families affected with rare X-linked recessive Hunter syndrome.
Screening of the IDS gene was performed in six individuals (three patients and their mothers) through whole genomic DNA extraction from peripheral blood followed by PCR and Sanger sequencing. MutationTaster, PROVEAN, Human Splicing Finder, Swiss-Model, and SwissPdbViewer were used for in silico analysis of identified variants.
All probands were presented with coarse facies, recurrent respiratory tract infection, and reduced IDS activity. Molecular screeningesult of nonsense-mediated mRNA decay. Our study provides the first genetic depiction of MPS-II in Pakistan, expands the global IDS mutation spectrum, may provide insights into the three-dimensional structure of IDS, and should benefit the affected families in genetic counseling and prenatal diagnosis.
The interaction of diet with gut microbiome has been implicated in the onset of cardiovascular disease. The gut microbiome displays diurnal rhythms, which may be influenced by meal timing.
This study aimed to investigate the effect of the timing of main meal consumption on the microbiome and cardiometabolic biomarkers of the host.
Seventeen healthy adults randomly consumed an isocaloric diet for 7 days, twice, by alternating lunch with dinner meals, and with a 2-week washout in-between. Sixty percent of the participants' daily energy requirements was consumed either as lunch or dinner, respectively. Meals were provided free to the participants. All fecal samples produced the last 3 days of each intervention were collected and analyzed for microbial profiling (16S rRNA gene amplicon sequencing), quantitative estimation of representative bacterial groups (qPCR) of the gut microbiome, and the output of short-chain fatty acids (SCFA) in feces. Fasted blood samples were analyzed for low-grade inflammatory biomarkers, blood lipids, insulin, and glucose levels. Cumulative energy loss in feces was measured over the collection period using bomb calorimetry.
Meal timing had no significant effects on fecal SCFA output, energy loss in feces, microbial community profiling, and bacterial species relative abundance. The absolute concentration of Escherichia coli was significantly higher after the large lunch intervention (p = 0.02). No effects on blood biomarkers of cardiometabolic health were observed.
In a well-controlled study, main meal timing displayed minimal acute effects on the gut microbiome composition, its diet-related function, and blood biomarkers of cardiometabolic health.
In a well-controlled study, main meal timing displayed minimal acute effects on the gut microbiome composition, its diet-related function, and blood biomarkers of cardiometabolic health.
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