greenmedinfo--2020-04-22--Nigella sativa exerts antibacterial, antiviral, anti-inflammatory, and wound healing properties.

It is estimated by the World Health Organization ( WHO ) that most of the world 's population depends on @ @ @ @ @ care.also known as black-caraway and as '' Kalonji , '' is a well-known seed all @ @ @ @ @ is one of the most common medicinal plants worldwide and contains many useful chemical constituents @ @ @ @ @ its fixed oil , such as thymoquinone , thymohydroquinone , dithymoquinone , thymol , nigellicine @ @ @ @ @ nigellicine , nigellidine , and alpha-hederin .
Due to these numerous important ingredients it was @ @ @ @ @ areas of our body and has many pharmacological effects as antibacterial , antiviral , anti-inflammatory @ @ @ @ @ and also for acne vulgaris , skin cancer , pigmentation , and many cosmeceutical applications @ @ @ @ @ usage ofseeds and oil , they are used in various systems of food and medicines @ @ @ @ @ article is to provide a detailed survey of the literature of cosmeceutical and external applications @ @ @ @ @ further studies on this subject .

It is estimated by the World Health Organization (WHO) that most of the world's population depends on herbal medicine for their health care.also known as black-caraway and as"Kalonji,"is a well-known seed all over the world. It is one of the most common medicinal plants worldwide and contains many useful chemical constituents that we can find in its fixed oil, such as thymoquinone, thymohydroquinone, dithymoquinone, thymol, nigellicine, carvacrol, nigellimine, nigellicine, nigellidine, and alpha-hederin. Due to these numerous important ingredients it was found that it affects different areas of our body and has many pharmacological effects as antibacterial, antiviral, anti-inflammatory, and wound healing effect and also for acne vulgaris, skin cancer, pigmentation, and many cosmeceutical applications. Based on the folklore usage ofseeds and oil, they are used in various systems of food and medicines. The aim of this article is to provide a detailed survey of the literature of cosmeceutical and external applications ofwhich is expected to stimulate further studies on this subject.


greenmedinfo--2020-04-22--This review will focus on vitamin D as a potential candidate to treat or prevent exacerbations in cy

This review will focus on vitamin D as a potential candidate to treat or prevent exacerbations in cystic fibrosis, COPD, and asthma.

Patients with respiratory diseases such as cystic fibrosis , chronic obstructive pulmonary disease , or asthma often experience an acute @ @ @ @ @ termed exacerbations .
Although the course of exacerbations is disease specific , they are mostly @ @ @ @ @ .
Exacerbations often require hospitalization and are an important cause of mortality .
Treatments of @ @ @ @ @ negative impact and to prevent subsequent events .
Despite many existing therapy options , many @ @ @ @ @ therapy and suffer from recurrent events .
Vitamin D deficiency is a worldwide problem and @ @ @ @ @ patients .
Vitamin D , known for its calcemic effects , also has immunomodulatory and @ @ @ @ @ be a possible agent to treat or prevent exacerbations .
This review will focus on @ @ @ @ @ candidate to treat or prevent exacerbations in CF , COPD , and asthma .

Patients with respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or asthma often experience an acute worsening of respiratory symptoms, termed exacerbations. Although the course of exacerbations is disease specific, they are mostly triggered by a respiratory infection. Exacerbations often require hospitalization and are an important cause of mortality. Treatments of exacerbations aim to minimize the negative impact and to prevent subsequent events. Despite many existing therapy options, many patients do not benefit from therapy and suffer from recurrent events. Vitamin D deficiency is a worldwide problem and is extremely prevalent in these patients. Vitamin D, known for its calcemic effects, also has immunomodulatory and anti-infectious actions and can therefore be a possible agent to treat or prevent exacerbations. This review will focus on vitamin D as a potential candidate to treat or prevent exacerbations in CF, COPD, and asthma.


greenmedinfo--2020-04-22--Borage oil consumption reduces transepidermal water loss and improves skin quality.

Human skin is not able to biosynthesize gamma-linolenic acid ( GLA , 18:3omega6 ) from the precursor linoleic acid ( LA ) , or arachidonic acid ( AA ) from dihomo-gamma-linolenic acid ( DHGLA ) .
Dietary supplementation with GLA-rich seed oil of borage skips the step of hepatic 6-desaturation of fatty acids ( FA ) and , therefore , compensates the lack of these essential FA in conditions with impaired activity of delta 6-desaturase .
Twenty-nine healthy elderly people ( mean age 68.6 years ) , received a daily dose of 360 or 720 mg GLA for 2 months @ @ @ @ @ @ @ ( Quintesal 180 , manufacturer Galderma Laboratorium GmbH , Freiburg , Germany ) .
The effects of fatty acids derived from ingested borage oil capsules on skin barrier function were assessed by measurement of transepidermal water loss ( TEWL ) .
The consumption of borage oil induced a statistically significant improvement of cutaneous barrier function in the elderly people , as reflected in a mean decrease of 10.8 % in the transepidermal water loss .
Thirty-four percent of the people noted itch before borage oil consumption and 0 % afterwards .
Dry skin @ @ @ @ @ @ @ to 14 % , but no significant alteration of skin hydration was measured .
The FA-composition of erythrocyte membrane phospholipids demonstrated an increase of GLA ( +70 % ) and DHGLA ( +18 % ) and a reduction of saturated and monounsaturated FA .
There was no significant alteration in nervonic acid or in AA content , but an increase in the DHGLA/AA ratio ( +23 % ) .
Thus , the consumption of borage oil by elderly people lead to alteration of FA metabolism and improved skin function .

Human skin is not able to biosynthesize gamma-linolenic acid (GLA, 18:3omega6) from the precursor linoleic acid (LA), or arachidonic acid (AA) from dihomo-gamma-linolenic acid (DHGLA). Dietary supplementation with GLA-rich seed oil of borage skips the step of hepatic 6-desaturation of fatty acids (FA) and, therefore, compensates the lack of these essential FA in conditions with impaired activity of delta 6-desaturase. Twenty-nine healthy elderly people (mean age 68.6 years), received a daily dose of 360 or 720 mg GLA for 2 months, using Borage oil in gelatine capsules (Quintesal 180, manufacturer Galderma Laboratorium GmbH, Freiburg, Germany). The effects of fatty acids derived from ingested borage oil capsules on skin barrier function were assessed by measurement of transepidermal water loss (TEWL). The consumption of borage oil induced a statistically significant improvement of cutaneous barrier function in the elderly people, as reflected in a mean decrease of 10.8% in the transepidermal water loss. Thirty-four percent of the people noted itch before borage oil consumption and 0% afterwards. Dry skin was claimed to be reduced from 42 to 14%, but no significant alteration of skin hydration was measured. The FA-composition of erythrocyte membrane phospholipids demonstrated an increase of GLA (+70%) and DHGLA (+18%) and a reduction of saturated and monounsaturated FA. There was no significant alteration in nervonic acid or in AA content, but an increase in the DHGLA/AA ratio (+23%). Thus, the consumption of borage oil by elderly people lead to alteration of FA metabolism and improved skin function.


greenmedinfo--2020-04-22--Dietary fatty acids modulate inflammatory gene expression in healthy humans.

Over the past 100 years , changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption , leading to a dramatic increase in the ratio of omega-6 ( omega6 ) to omega3 polyunsaturated fatty acids ( PUFA ) in circulation and in tissues .
Increased omega6/omega3 ratios are hypothesized to increase inflammatory mediator production , leading to higher incidence of inflammatory diseases , and may impact inflammatory gene expression .
To determine the effect of reducing the omega6/omega3 ratio on expression of inflammatory pathway genes in mononuclear cells , healthy humans were placed @ @ @ @ @ @ @ , then given fish oil and borage oil for an additional 4 weeks .
Serum and neutrophil fatty acid composition and ex vivo leukotriene B ( 4 ) production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout .
RNA was isolated from mononuclear cells and expression of PI3K , Akt , NFkappaB , and inflammatory cytokines was measured by real-time PCR .
A marked increase was seen in serum and neutrophil levels of long-chain omega3 PUFA concomitant with a reduction in the @ @ @ @ @ @ @ .
The ex vivo capacity of stimulated neutrophils to produce leukotriene B ( 4 ) was decreased by 31 % .
Expression of PI3Kalpha and PI3Kgamma and the quantity of PI3Kalpha protein in mononuclear cells was reduced after supplementation , as was the expression of several proinflammatory cytokines .
These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines .

Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (omega6) to omega3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased omega6/omega3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the omega6/omega3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B(4) production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NFkappaB, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain omega3 PUFA concomitant with a reduction in the omega6/omega3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B(4) was decreased by 31%. Expression of PI3Kalpha and PI3Kgamma and the quantity of PI3Kalpha protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.


greenmedinfo--2020-04-22--Association between serum vitamin D and chronic rhinosinusitis: a meta-analysis.

INTRODUCTION : Chronic rhinosinusitis is a highly heterogeneous chronic inflammation of the upper respiratory tract caused by immune dysfunction in human beings .
However , the underlying etiology of this disease has not yet been well established .
Several trials have revealed that serum vitamin D level abnormality might play a role in the pathophysiology of chronic rhinosinusitis .
OBJECTIVE : The aim of present study was to perform a meta-analysis of studies to compare the serum vitamin D levels between patients with chronic rhinosinusitis and healthy controls and to evaluate the potential associations of serum vitamin D level with @ @ @ @ @ @ @ : Following the PRISMA guidelines , relevant databases incorporating Pubmed , Web of Science , Embase and Cochrane Library were searched from inception to December 1 , 2018 .
Funnel plot symmetry and Egger ' test were used to detect publication biases .
The outcomes were presented as Weighted Mean Difference combined with 95 % Confidence Intervals to estimate the difference of serum vitamin D levels between patients with chronic rhinosinusitis and controls .
Higgins Ivalue was used to test for heterogeneity between the included studies .
RESULTS : Out of 176 studies @ @ @ @ @ @ @ rhinosinusitis patients and 179 healthy controls met the criteria and were included in the meta-analysis .
In a pooled analysis of the studies , chronic rhinosinusitis patients showed decreased serum vitamin D status ( WMD = -7.80 , 95 % CI -13.28 to -2.31 , p = 0.000 ) .
Subgroups analyses based on study location ( USA vs. Non-USA ) , types of biomarkers ( 25 ( OH ) D3 vs. 25 ( OH ) D ) and the study design methods ( retrospective vs. prospective ) did not reveal heterogeneity .
@ @ @ @ @ @ @ with versus without polyposis might account for some degree of heterogeneity .
Meanwhile , a lower serum vitamin D level was observed in chronic rhinosinusitis with nasal polyps patients .
CONCLUSION : Our findings indicate that serum vitamin D level might be associated with patients with chronic rhinosinusitis as we detected a significant association between lower serum vitamin D status and chronic rhinosinusitis , especially in chronic rhinosinusitis with nasal polyps patients .
However , further comprehensive studies are warranted in order to draw firm conclusions .

INTRODUCTION: Chronic rhinosinusitis is a highly heterogeneous chronic inflammation of the upper respiratory tract caused by immune dysfunction in human beings. However, the underlying etiology of this disease has not yet been well established. Several trials have revealed that serum vitamin D level abnormality might play a role in the pathophysiology of chronic rhinosinusitis.
OBJECTIVE: The aim of present study was to perform a meta-analysis of studies to compare the serum vitamin D levels between patients with chronic rhinosinusitis and healthy controls and to evaluate the potential associations of serum vitamin D level with the occurrence of chronic rhinosinusitis.
METHODS: Following the PRISMA guidelines, relevant databases incorporating Pubmed, Web of Science, Embase and Cochrane Library were searched from inception to December 1, 2018. Funnel plot symmetry and Egger' test were used to detect publication biases. The outcomes were presented as Weighted Mean Difference combined with 95% Confidence Intervals to estimate the difference of serum vitamin D levels between patients with chronic rhinosinusitis and controls. Higgins Ivalue was used to test for heterogeneity between the included studies.
RESULTS: Out of 176 studies, only eight studies involving 337 chronic rhinosinusitis patients and 179 healthy controls met the criteria and were included in the meta-analysis. In a pooled analysis of the studies, chronic rhinosinusitis patients showed decreased serum vitamin D status (WMD = -7.80, 95% CI -13.28 to -2.31, p = 0.000). Subgroups analyses based on study location (USA vs. Non-USA), types of biomarkers (25(OH)D3 vs. 25(OH)D) and the study design methods (retrospective vs. prospective) did not reveal heterogeneity. However, phenotypes of chronic rhinosinusitis, with versus without polyposis might account for some degree of heterogeneity. Meanwhile, a lower serum vitamin D level was observed in chronic rhinosinusitis with nasal polyps patients.
CONCLUSION: Our findings indicate that serum vitamin D level might be associated with patients with chronic rhinosinusitis as we detected a significant association between lower serum vitamin D status and chronic rhinosinusitis, especially in chronic rhinosinusitis with nasal polyps patients. However, further comprehensive studies are warranted in order to draw firm conclusions.


greenmedinfo--2020-04-22--Borage oil protects DNA, modulates oxidative stress, and exerts anticancer activity.

Borage ( Borago officinalis L. ) seed oil has been used as a treatment for various degenerative diseases .
Many useful properties of this oil are attributed to its high gamma linolenic acid content ( GLA , 18:3ω-6 ) .
The purpose of this study was to demonstrate the safety and suitability of the use of borage seed oil , along with one of its active components , GLA , with respect to DNA integrity , and to establish possible in vivo toxic and in vitro cytotoxic effects .
In order to measure these properties , five types of assays @ @ @ @ @ @ @ , antigenotoxicity , cytotoxicity ( using the promyelocytic leukaemia HL60 cell line ) , and life span ( in vivo analysis using the Drosophila model ) .
Results showed that i ) Borage seed oil is not toxic to D. melanogaster at physiological concentrations below 125 µl/ml and the studies on GLA indicated non-toxicity at the lowest concentration analyzed ii ) Borage seed oil and GLA are DNA safe ( non-genotoxic ) and antimutagenic compared to hydrogen peroxide , thereby confirming its antioxidant capacity ; iii ) Borage seed oil and GLA exhibited @ @ @ @ @ @ @ of 1 µl/ml and 0.087 mM , respectively ) iv ) Low doses of borage seed oil ( 0.19 % ) increased the health span of D. melanogaster ; and v ) GLA significantly decreased the life span of D. melanogaster.Based on the antimutagenic and cytotoxic effects along with the ability to increase the health span , we propose supplementation with borage seed oil rather than GLA , because it protects DNA by modulating oxidative genetic damage in D. melanogaster , increases the health span and exerts cytotoxic activity towards promyelocytic HL60 cells @

Borage (Borago officinalis L.) seed oil has been used as a treatment for various degenerative diseases. Many useful properties of this oil are attributed to its high gamma linolenic acid content (GLA, 18:3ω-6). The purpose of this study was to demonstrate the safety and suitability of the use of borage seed oil, along with one of its active components, GLA, with respect to DNA integrity, and to establish possible in vivo toxic and in vitro cytotoxic effects. In order to measure these properties, five types of assays were carried out: toxicity, genotoxicity, antigenotoxicity, cytotoxicity (using the promyelocytic leukaemia HL60 cell line), and life span (in vivo analysis using the Drosophila model). Results showed that i) Borage seed oil is not toxic to D. melanogaster at physiological concentrations below 125 µl/ml and the studies on GLA indicated non-toxicity at the lowest concentration analyzed ii) Borage seed oil and GLA are DNA safe (non-genotoxic) and antimutagenic compared to hydrogen peroxide, thereby confirming its antioxidant capacity; iii) Borage seed oil and GLA exhibited cytotoxic activity in low doses (IC50 of 1 µl/ml and 0.087 mM, respectively) iv) Low doses of borage seed oil (0.19%) increased the health span of D. melanogaster; and v) GLA significantly decreased the life span of D. melanogaster.Based on the antimutagenic and cytotoxic effects along with the ability to increase the health span, we propose supplementation with borage seed oil rather than GLA, because it protects DNA by modulating oxidative genetic damage in D. melanogaster, increases the health span and exerts cytotoxic activity towards promyelocytic HL60 cells.


greenmedinfo--2020-04-22--Nanoparticular thymoquinone attenuates angiogenesis and metastasis of triple-negative breast cancer.

Triple-negative breast cancer ( TNBC ) is a highly aggressive and metastatic subtype of breast cancer showing non-responsiveness to most available therapeutic options .
Therefore , smart therapeutic approaches to selectively transport and target TNBCs are required .
Herein , we developed thymoquinone ( TQ ) -loaded , hyaluronic acid ( HA ) -conjugated Pluronic® P123 and F127 copolymer nanoparticles ( HA-TQ-Nps ) as a selective drug-carrying vehicle to deliver anticancer phytochemical TQ to TNBC cells .
The mean size of nanoparticles was around 19.3 ± 3.2 nm .
and they were stable at room temperature up to 4 months @ @ @ @ @ @ @ cells but did not show the toxic effect on normal cells .
Detailed investigations also demonstrated its pro-apoptotic , anti-metastatic and anti-angiogenic activity .
In-depth mechanistic studies highlighted that HA-TQ-Nps retarded cell migration of TNBC cells through up-regulation of microRNA-361 which in turn down-regulated Rac1 and RhoA mediated cell migration and also perturbed the cancer cell migration under the influence of the autocrine effect of VEGF-A .
Moreover , HA-TQ-Np-treatment also perturbed tumor-induced vascularization by reducing the secretion of VEGF-A .
The anti-metastatic and anti-angiogenic activity of HA-TQ-Nps was found to be evident @ @ @ @ @ @ @ 4T1-mammary solid tumor model in syngeneic mice .
Thus , an innovative targeted nano-therapeutic approach is being established to reduce the tumor burden and inhibit metastasis and angiogenesis simultaneously for better management of TNBC .

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic subtype of breast cancer showing non-responsiveness to most available therapeutic options. Therefore, smart therapeutic approaches to selectively transport and target TNBCs are required. Herein, we developed thymoquinone (TQ)-loaded, hyaluronic acid (HA)-conjugated Pluronic® P123 and F127 copolymer nanoparticles (HA-TQ-Nps) as a selective drug-carrying vehicle to deliver anticancer phytochemical TQ to TNBC cells. The mean size of nanoparticles was around 19.3 ± 3.2 nm. and they were stable at room temperature up to 4 months. HA-TQ-Nps were immensely cytotoxic towards TNBC cells but did not show the toxic effect on normal cells. Detailed investigations also demonstrated its pro-apoptotic, anti-metastatic and anti-angiogenic activity. In-depth mechanistic studies highlighted that HA-TQ-Nps retarded cell migration of TNBC cells through up-regulation of microRNA-361 which in turn down-regulated Rac1 and RhoA mediated cell migration and also perturbed the cancer cell migration under the influence of the autocrine effect of VEGF-A. Moreover, HA-TQ-Np-treatment also perturbed tumor-induced vascularization by reducing the secretion of VEGF-A. The anti-metastatic and anti-angiogenic activity of HA-TQ-Nps was found to be evident in both MDA-MB-231 xenograft chick embryos and 4T1-mammary solid tumor model in syngeneic mice. Thus, an innovative targeted nano-therapeutic approach is being established to reduce the tumor burden and inhibit metastasis and angiogenesis simultaneously for better management of TNBC.


greenmedinfo--2020-04-22--Natural substances such as Aloe vera, cinnamon, green tea, fenugreek, and silymarin can be used as a

Background Polycystic Ovary Syndrome ( PCOS ) is one of the most common endocrine abnormalities in women .
Due to the side effects of drugs , the tendency to use natural antioxidants and anti-inflammatory agents to regulate metabolism , hyperinsulinemia , and hyperlipidemia in PCOS patients has been increased .
This review aimed to investigate the role of herbal substances on the treatment of PCOS .
Methods The present review was carried out using keywords such as polycystic ovary syndrome and/or PCOS and/or herb .
Databases including Web of Science , PubMed , and Science Direct were used to collect @ @ @ @ @ @ @ 2019 .
We excluded studies unrelated to the PCOS and medical herbs .
Results Overall , 361 records were identified through database searching .
After primary screening and the full-texts assessment , 323 records were excluded , and 38 articles were finally included .
The results indicate that some medicinal herbs may have a key role in treating PCOS .
The compounds in these medical herbs can affect lipid profiles ( Aloe vera , chamomile , and cinnamon ) , insulin resistance ( cinnamon , chamomile , Aloe vera , and Camellia sinensis @ @ @ @ @ @ @ , cinnamon , and Camellia sinensis ) , hormones ( Aloe vera , silymarin , chamomile , fenugreek , Camellia sinensis , Heracleum persicum , Potentilla , Mentha spicata , Foeniculum vulgar , licorice , and Marrubium ) , and ovarian tissue ( Aloe vera , chamomile , Camellia sinensis , Mentha spicata , and silymarin ) .
Conclusion Natural substances such as Aloe vera , cinnamon , green tea , fenugreek , and silymarin can be used as a new supportive care for PCOS .
Further clinical trials are warranted to confirm @ @ @ @ @

Background Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine abnormalities in women. Due to the side effects of drugs, the tendency to use natural antioxidants and anti-inflammatory agents to regulate metabolism, hyperinsulinemia, and hyperlipidemia in PCOS patients has been increased. This review aimed to investigate the role of herbal substances on the treatment of PCOS. Methods The present review was carried out using keywords such as polycystic ovary syndrome and/or PCOS and/or herb. Databases including Web of Science, PubMed, and Science Direct were used to collect all related articles published from 1990 to 2019. We excluded studies unrelated to the PCOS and medical herbs. Results Overall, 361 records were identified through database searching. After primary screening and the full-texts assessment, 323 records were excluded, and 38 articles were finally included. The results indicate that some medicinal herbs may have a key role in treating PCOS. The compounds in these medical herbs can affect lipid profiles (Aloe vera, chamomile, and cinnamon), insulin resistance (cinnamon, chamomile, Aloe vera, and Camellia sinensis), blood glucose (Aloe vera, cinnamon, and Camellia sinensis), hormones (Aloe vera, silymarin, chamomile, fenugreek, Camellia sinensis, Heracleum persicum, Potentilla, Mentha spicata, Foeniculum vulgar, licorice, and Marrubium), and ovarian tissue (Aloe vera, chamomile, Camellia sinensis, Mentha spicata, and silymarin). Conclusion Natural substances such as Aloe vera, cinnamon, green tea, fenugreek, and silymarin can be used as a new supportive care for PCOS. Further clinical trials are warranted to confirm their benefits and safety.


greenmedinfo--2020-04-22--Turmeric: A Natural Remedy for Children and Teens with Asthma

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greenmedinfo--2020-04-22--Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib  leading to

Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib  leading to inhibition of EMT in human lung cancer.

HOTAIR is an important carcinogenic lncRNA and involves in tumorigenesis , and invasion .
MiR-34a-5p functions as a tumour suppressor .
However , the underlying mechanism of HOTAIR regulation especially in association with miR-34a-5p in non-small-cell lung cancer ( NSCLC ) has not been explored .
Herein , we performed series of in vitro experiments , including viability , migration , invasion , apoptosis and in vivo xenograft model , and identified that HOTAIR was remarkably elevated in NSCLC cells .
Enforced HOTAIR expression promoted migration and invasion , while depleted HOTAIR diminished the ability of migration and invasion of @ @ @ @ @ @ @ miR-34a-5p was dramatically inhibited in NSCLC cells and the binding correlation between HOTAIR and miR-34a-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays .
We also showed that induction of miR-34a-5p and reduction of HOTAIR , and the interaction between miR-34a-5p and HOTAIR resulted in the suppression of epithelial-mesenchymal transition ( EMT ) as illustrated by induction of key epithelial markers E-cadherin expression , reduction of vimentin and EMT-inducing transcription factor snail .
Excessive expression of snail resisted miR-34a-5p-inhibited cell growth .
Snail binds to E-cadherin promoter and regulates E-cadherin expression .
@ @ @ @ @ @ @ berberine and gefinitib in this process .
Similar findings were also observed in a tumour xenograft model .
Collectively , this is the first report demonstrating reciprocal interaction of miR-34a-5p- and HOTAIR-mediated regulation of snail resulting in inhibition of EMT process by the combination of berberine and gefitinib suggesting that regulation of miR-34a-5p- and HOTAIR-mediated inhibition of EMT may provide novel treatment paradigms for lung cancer .

HOTAIR is an important carcinogenic lncRNA and involves in tumorigenesis, and invasion. MiR-34a-5p functions as a tumour suppressor. However, the underlying mechanism of HOTAIR regulation especially in association with miR-34a-5p in non-small-cell lung cancer (NSCLC) has not been explored. Herein, we performed series of in vitro experiments, including viability, migration, invasion, apoptosis and in vivo xenograft model, and identified that HOTAIR was remarkably elevated in NSCLC cells. Enforced HOTAIR expression promoted migration and invasion, while depleted HOTAIR diminished the ability of migration and invasion of NSCLC cells. We also observed that miR-34a-5p was dramatically inhibited in NSCLC cells and the binding correlation between HOTAIR and miR-34a-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. We also showed that induction of miR-34a-5p and reduction of HOTAIR, and the interaction between miR-34a-5p and HOTAIR resulted in the suppression of epithelial-mesenchymal transition (EMT) as illustrated by induction of key epithelial markers E-cadherin expression, reduction of vimentin and EMT-inducing transcription factor snail. Excessive expression of snail resisted miR-34a-5p-inhibited cell growth. Snail binds to E-cadherin promoter and regulates E-cadherin expression. There was a synergy in combination of berberine and gefinitib in this process. Similar findings were also observed in a tumour xenograft model. Collectively, this is the first report demonstrating reciprocal interaction of miR-34a-5p- and HOTAIR-mediated regulation of snail resulting in inhibition of EMT process by the combination of berberine and gefitinib suggesting that regulation of miR-34a-5p- and HOTAIR-mediated inhibition of EMT may provide novel treatment paradigms for lung cancer.


greenmedinfo--2020-04-22--Berberine attenuates Aβ42-induced neuronal damage through regulating circHDAC9/miR-142-5p axis in hu

Berberine attenuates Aβ42-induced neuronal damage through regulating circHDAC9/miR-142-5p axis in human neuronal cells.

BACKGROUND : Berberine plays a neuroprotective role in neurodegenerative diseases , including Alzheimer 's disease ( AD ) .
Circular RNAs ( circRNAs ) function as crucial players in AD pathogenesis .
In the current work , we aimed to investigate whether circRNA histone deacetylase 9 ( circHDAC9 ) was involved in the regulation of berberine in AD .
METHODS : Cell viability and apoptosis were determined by the Cell Counting Kit-8 ( CCK-8 ) assay and flow cytometry , respectively .
Enzyme-linked immunosorbent assay ( ELISA ) was used to assess caspase-3 activity and the production of interleukin-1β ( @ @ @ @ @ @ @ factor-α ( TNF-α ) .
The levels of circHDAC9 and miR-142-5p were detected by quantitative real-time polymerase chain reaction ( qRT-PCR ) .
Subcellular fractionation assays were performed to evaluate the localization of circHDAC9 .
The direct interaction between circHDAC9 and miR-142-5p was confirmed by dual-luciferase reporter , RNA immunoprecipitation ( RIP ) and RNA pull-down assays .
RESULTS : Our data indicated that circHDAC9 was indeed a circular transcript and mainly localized in the cytoplasm .
42-residueβ-amyloid ( Aβ42 ) triggered a significant down-regulation in circHDAC9 and a striking up-regulation in miR-142-5p @ @ @ @ @ @ @ .
Berberine relieved Aβ42-induced HN cell neurotoxicity .
Moreover , berberine resulted in increased circHDAC9 expression and decreased miR-142-5p level in Aβ42-treated HN cells .
Berberine alleviated Aβ42-induced neuronal damage in HN cells by up-regulating circHDAC9 .
Furthermore , circHDAC9 acted as a molecular sponge of miR-142-5p .
CircHDAC9 overexpression alleviated Aβ42-induced HN cell neurotoxicity via miR-142-5p .
CONCLUSION : Our current study suggested that berberine protected HN cell from Aβ42-induced neuronal damage at least partly through regulating the circHDAC9/miR-142-5p axis , highlighting novel evidence for the neuroprotective effect of berberine in AD @

BACKGROUND: Berberine plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease (AD). Circular RNAs (circRNAs) function as crucial players in AD pathogenesis. In the current work, we aimed to investigate whether circRNA histone deacetylase 9 (circHDAC9) was involved in the regulation of berberine in AD.
METHODS: Cell viability and apoptosis were determined by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to assess caspase-3 activity and the production of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). The levels of circHDAC9 and miR-142-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular fractionation assays were performed to evaluate the localization of circHDAC9. The direct interaction between circHDAC9 and miR-142-5p was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays.
RESULTS: Our data indicated that circHDAC9 was indeed a circular transcript and mainly localized in the cytoplasm. 42-residueβ-amyloid (Aβ42) triggered a significant down-regulation in circHDAC9 and a striking up-regulation in miR-142-5p in human neuronal (HN) cells. Berberine relieved Aβ42-induced HN cell neurotoxicity. Moreover, berberine resulted in increased circHDAC9 expression and decreased miR-142-5p level in Aβ42-treated HN cells. Berberine alleviated Aβ42-induced neuronal damage in HN cells by up-regulating circHDAC9. Furthermore, circHDAC9 acted as a molecular sponge of miR-142-5p. CircHDAC9 overexpression alleviated Aβ42-induced HN cell neurotoxicity via miR-142-5p.
CONCLUSION: Our current study suggested that berberine protected HN cell from Aβ42-induced neuronal damage at least partly through regulating the circHDAC9/miR-142-5p axis, highlighting novel evidence for the neuroprotective effect of berberine in AD.


greenmedinfo--2020-04-22--Mechanisms of berberine for the treatment of atherosclerosis based on network pharmacology.

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder .
The processes of atherosclerosis include endothelial dysfunction , new endothelial layer formation , lipid sediment , foam cell formation , plaque formation , and plaque burst .
Owing to the adverse effects of first-line medications , it is urgent to discover new medications to deal with atherosclerosis .
Berberine is one of the most promising natural products derived from traditional Chinese medicine .
However , the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly .
In this study , we used network pharmacology to investigate @ @ @ @ @ @ @ We identified potential targets related to berberine and atherosclerosis from several databases .
A total of 31 and 331 putative targets for berberine and atherosclerosis were identified , respectively .
Then , we constructed berberine and atherosclerosis targets with PPI data .
Berberine targets network with PPI data had 3204 nodes and 79437 edges .
Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges .
Furthermore , we merged the two PPI networks and obtained the core PPI network from the merged PPI network .
The core PPI network had @ @ @ @ @ @ @ last , we performed functional enrichment analyses including GO and KEGG pathway analysis in David database .
GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle .
KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle , ubiquitin mediated proteolysis , MAPK signaling pathway , and PI3K-Akt signaling pathway .
After combining the results in context with the available treatments for atherosclerosis , we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis .
Our @ @ @ @ @ @ @ future research .

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder. The processes of atherosclerosis include endothelial dysfunction, new endothelial layer formation, lipid sediment, foam cell formation, plaque formation, and plaque burst. Owing to the adverse effects of first-line medications, it is urgent to discover new medications to deal with atherosclerosis. Berberine is one of the most promising natural products derived from traditional Chinese medicine. However, the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly. In this study, we used network pharmacology to investigate the interaction between berberine and atherosclerosis. We identified potential targets related to berberine and atherosclerosis from several databases. A total of 31 and 331 putative targets for berberine and atherosclerosis were identified, respectively. Then, we constructed berberine and atherosclerosis targets with PPI data. Berberine targets network with PPI data had 3204 nodes and 79437 edges. Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges. Furthermore, we merged the two PPI networks and obtained the core PPI network from the merged PPI network. The core PPI network had 132 nodes and 3339 edges. At last, we performed functional enrichment analyses including GO and KEGG pathway analysis in David database. GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle. KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle, ubiquitin mediated proteolysis, MAPK signaling pathway, and PI3K-Akt signaling pathway. After combining the results in context with the available treatments for atherosclerosis, we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis. Our study provided a valid theoretical foundation for future research.


greenmedinfo--2020-04-22--Berberine inhibits MDA-MB-231 cells by attenuating their inflammatory responses.

Breast cancer initiation is closely associated with cytokines that can change the inflammatory tumor microenvironment .
Compounds extracted from plants @ @ @ @ @ possibility of cancer treatment in the recent decades .
Berberine is an isoquinoline plant alkaloid @ @ @ @ @ roles , which is used in ethnic medicines , including traditional Chinese and North American @ @ @ @ @ study , we investigated the effects of berberine on the malignant tumor cell behaviors in @ @ @ @ @ MDA-MB-231 .
We found that berberine could not influence the cell viability in normal condition @ @ @ @ @ the cancer cell migration capability in a scratch wound model and accordingly prolong the wound @ @ @ @ @ our results demonstrated that berberine inhibited the increased phosphorylation of c-Jun and c-Fos in these @ @ @ @ @ the cotreatment with LPS , which could boost the expression of cytokines in these cancer @ @ @ @ @ the increased expression of TNF-and IL-6 .
Meanwhile , we found that berberine inhibited the @ @ @ @ @ the degradation of IB .

Breast cancer initiation is closely associated with cytokines that can change the inflammatory tumor microenvironment. Compounds extracted from plants have been explored for the possibility of cancer treatment in the recent decades. Berberine is an isoquinoline plant alkaloid with remarkable antioxidant and anti-inflammation roles, which is used in ethnic medicines, including traditional Chinese and North American medicine. In the present study, we investigated the effects of berberine on the malignant tumor cell behaviors in a breast cell line, MDA-MB-231. We found that berberine could not influence the cell viability in normal condition but was able to decrease the cancer cell migration capability in a scratch wound model and accordingly prolong the wound healing time. Furthermore, our results demonstrated that berberine inhibited the increased phosphorylation of c-Jun and c-Fos in these scratched cancer cells. With the cotreatment with LPS, which could boost the expression of cytokines in these cancer cells, berberine significantly reduced the increased expression of TNF-and IL-6. Meanwhile, we found that berberine inhibited the activation of NF-B by preventing the degradation of IB.


greenmedinfo--2020-04-22--Berberine inhibits human gastric cancer cell growth.

PURPOSE : Gastric cancer accounts for considerable mortality across the globe .
In this study the anticancer effects of a natural compound Berberine were investigated in vitro .
Effects of berberine on cell migration , cellular apoptosis , Nf-kB and JNK/p38 signalling pathways were also studied .
METHODS : The cell viability of SNU-1 gastric cancer cells after berberine treatment was evaluated by CCK-8 assay , while the effects on cell migration were checked by wound healing assay .
Effects on cellular apoptosis were evaluated by fluorescence microscopy using DAPI staining , as well as using flow cytometry with annexin @ @ @ @ @ @ @ Effects on apoptosis-related protein expressions were checked by western blot method .
RESULTS : The results showed that Berberine decreased the viability of the gastric cancer SNU-1 cells and exhibited an IC50 of 30µM .
The cytoxicity of Berberine was also investigated on the normal GES-1 gastric cells and it was found that Berberine exerted very low toxic effects on these cells and exhibited an IC50 of 120 µM .
Berberine also caused remarkable changes in the morphology of the SNU-1 cells .
PI and DAPI stainingrevealed that Berberine prompted apoptosis of the @ @ @ @ @ @ @ The apoptotic cells increased from 2.2 % in control to around 35 % at 30 µM concentration .
Berberine also suppressed the migration and invasion of the gastric cancer cells via blocking of the JNK/p38 signallingpathway .
CONCLUSIONS : Berberine may act as a promising drug candidate for gastric cancer as demonstrated from the current study .

PURPOSE: Gastric cancer accounts for considerable mortality across the globe. In this study the anticancer effects of a natural compound Berberine were investigated in vitro. Effects of berberine on cell migration, cellular apoptosis, Nf-kB and JNK/p38 signalling pathways were also studied.
METHODS: The cell viability of SNU-1 gastric cancer cells after berberine treatment was evaluated by CCK-8 assay, while the effects on cell migration were checked by wound healing assay. Effects on cellular apoptosis were evaluated by fluorescence microscopy using DAPI staining, as well as using flow cytometry with annexin V/propidium iodide (PI) staining. Effects on apoptosis-related protein expressions were checked by western blot method.
RESULTS: The results showed that Berberine decreased the viability of the gastric cancer SNU-1 cells and exhibited an IC50 of 30µM. The cytoxicity of Berberine was also investigated on the normal GES-1 gastric cells and it was found that Berberine exerted very low toxic effects on these cells and exhibited an IC50 of 120 µM. Berberine also caused remarkable changes in the morphology of the SNU-1 cells. PI and DAPI stainingrevealed that Berberine prompted apoptosis of the SNU-1 cells in a dose-dependent manner. The apoptotic cells increased from 2.2% in control to around 35% at 30 µM concentration. Berberine also suppressed the migration and invasion of the gastric cancer cells via blocking of the JNK/p38 signallingpathway.
CONCLUSIONS: Berberine may act as a promising drug candidate for gastric cancer as demonstrated from the current study.


greenmedinfo--2020-04-22--Ginger Helps Relieve Inflammation Caused by Rheumatoid Arthritis


greenmedinfo--2020-04-22--Adhesion-related immunomodulatory activity of the screened Lactobacillus plantarum from sichuan pick

Adhesion-related immunomodulatory activity of the screened Lactobacillus plantarum from sichuan pickle.

Lactic acid bacteria are the majority fermentation starter in the traditional fermented foods .
In this research , a promising @ @ @ @ @ Sichuan pickle and its adhesion properties were analyzed in simulated gastrointestinal fluid with different methods @ @ @ @ @ effect of this strain was also evaluated in the Caco-2 cells .
Results found that @ @ @ @ @ genes like lsp and tuf were upregulated in different culture times .
Furthermore , L. @ @ @ @ @ revealed some anti-inflammation activity through inhibited expression of cytokine IL-8 and increased expression of anti-inflammatory @ @ @ @ @ .
The texture of yogurt after fermented by this kind of isolated strain was also @ @ @ @ @ foundation for the further development and application of this kind of strain in food production @ @ @ @ @ be carried out to determine whether this probiotic contributes to regulation of intestinal flora and @ @ @ @ @

Lactic acid bacteria are the majority fermentation starter in the traditional fermented foods. In this research, a promising Lactobacillus plantarum was isolated from Sichuan pickle and its adhesion properties were analyzed in simulated gastrointestinal fluid with different methods. Meanwhile, the immunomodulatory effect of this strain was also evaluated in the Caco-2 cells. Results found that adhesion-related mub genes and other genes like lsp and tuf were upregulated in different culture times. Furthermore, L. plantarum cultured at alkaline environment revealed some anti-inflammation activity through inhibited expression of cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in Caco-2 cells. The texture of yogurt after fermented by this kind of isolated strain was also investigated, which provides the foundation for the further development and application of this kind of strain in food production. More investigations need to be carried out to determine whether this probiotic contributes to regulation of intestinal flora and prevention of gut inflammation.


greenmedinfo--2020-04-22--These results recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaric

These results recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaricus 151 and S. thermophiles.

We investigated the yogurt starter cultures of Lactobacillus bulgaricus 151 and Streptococcus thermophilus MK-10 for their effect on the severity of experimental colitis , lymphocyte profile , and regulatory T-cell response .
Colitis was induced in BALB/c mice via the administration of 3.5 % dextran sulfate sodium salt ( DSS ) in drinking water for 6 d. Next , the mice were gavaged intragastrically with an active yogurt cultures ( YC ) mixture ( ∼5 × 10cfu/mouse per day ) or saline ( vehicle ) for 8 d. Mice receiving DSS or saline alone served as positive and negative controls @ @ @ @ @ @ @ colon , disease activity index , histological scores , myeloperoxidase activity , epithelium-associated microbes , short-chain fatty acid profile , total IgA antibody-forming cells , CD3CD8 , CD3CD4 , CD3CD4CD25 , CD3CD4CD25Foxp3T-cell subsets , and cytokine profiles ( IL-2 , IL-4 , IL-6 , IL-10 , IL-17A , IFN-γ , and tumor necrosis factor ) were examined after termination of the mice .
Feeding mice with YC mixture reduced disease symptoms and modified intestinal microbiota and host inflammatory responsiveness to DSS .
We observed limited weight loss and a decreased disease activity index @ @ @ @ @ @ @ somewhat reduced damage of the intestine .
The YC mixture upregulated the colon length , increased the amount and diversity of mucosa-associated microbes ( enterobacteria , enterococci , and yeast ) , and decreased the concentration of putrefactive short-chain fatty acids in the cecal contents .
It downregulated the input of cytotoxic CD3CD8T cells and CD3CD4CD25FoxP3regulatory T cells in Peyer 's patches and enhanced CD3CD4CD25T cells in spleens and CD3CD4CD25FoxP3cells in peripheral blood mononuclear cells .
Simultaneously , IgA antibody-forming cells were downregulated in mesenteric lymph nodes ( MLN ) and enhanced in @ @ @ @ @ @ @ mostly enhanced the production of cytokines tested in MLN and SPL , except for IL-6 , which was downregulated in MLN .
Interleukin-2 and IL-4 were the most upregulated in MLN , whereas IL-10 , IL-4 , IL-2 , IFN-γ , and tumor necrosis factor were most upregulated in SPL .
In serum , the YC mixture downregulated IFN-γ and clearly increased IL-2 .
Based on these results , we recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaricus 151 and S. thermophilus MK-10 set .
The strains possess the ability @ @ @ @ @ @ @ immune system toward both IgA production and induction of regulatory T cells , shifting Th1/Th2 balance .

We investigated the yogurt starter cultures of Lactobacillus bulgaricus 151 and Streptococcus thermophilus MK-10 for their effect on the severity of experimental colitis, lymphocyte profile, and regulatory T-cell response. Colitis was induced in BALB/c mice via the administration of 3.5% dextran sulfate sodium salt (DSS) in drinking water for 6 d. Next, the mice were gavaged intragastrically with an active yogurt cultures (YC) mixture (∼5 × 10cfu/mouse per day) or saline (vehicle) for 8 d. Mice receiving DSS or saline alone served as positive and negative controls, respectively. The length of the colon, disease activity index, histological scores, myeloperoxidase activity, epithelium-associated microbes, short-chain fatty acid profile, total IgA antibody-forming cells, CD3CD8, CD3CD4, CD3CD4CD25, CD3CD4CD25Foxp3T-cell subsets, and cytokine profiles (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and tumor necrosis factor) were examined after termination of the mice. Feeding mice with YC mixture reduced disease symptoms and modified intestinal microbiota and host inflammatory responsiveness to DSS. We observed limited weight loss and a decreased disease activity index score, lowered myeloperoxidase activity, and somewhat reduced damage of the intestine. The YC mixture upregulated the colon length, increased the amount and diversity of mucosa-associated microbes (enterobacteria, enterococci, and yeast), and decreased the concentration of putrefactive short-chain fatty acids in the cecal contents. It downregulated the input of cytotoxic CD3CD8T cells and CD3CD4CD25FoxP3regulatory T cells in Peyer's patches and enhanced CD3CD4CD25T cells in spleens and CD3CD4CD25FoxP3cells in peripheral blood mononuclear cells. Simultaneously, IgA antibody-forming cells were downregulated in mesenteric lymph nodes (MLN) and enhanced in spleens (SPL). The cultures mostly enhanced the production of cytokines tested in MLN and SPL, except for IL-6, which was downregulated in MLN. Interleukin-2 and IL-4 were the most upregulated in MLN, whereas IL-10, IL-4, IL-2, IFN-γ, and tumor necrosis factor were most upregulated in SPL. In serum, the YC mixture downregulated IFN-γ and clearly increased IL-2. Based on these results, we recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaricus 151 and S. thermophilus MK-10 set. The strains possess the ability to modulate the intestinal mucosal and systemic immune system toward both IgA production and induction of regulatory T cells, shifting Th1/Th2 balance.


greenmedinfo--2020-04-23--The complex role of vitamin D in autoimmune diseases.

Vitamin D , besides having well-known control functions of calcium and phosphorus metabolism , bone formation and mineralization , also @ @ @ @ @ maintenance of immune-homeostasis .
The immune-regulatory role of vitamin D affects both the innate and @ @ @ @ @ the immune-tolerance of self-structures .
Impaired vitamin D supply/regulation , amongst other factors , leads @ @ @ @ @ processes in animal models of various autoimmune diseases .
The administration of vitamin D in @ @ @ @ @ of immune-mediated symptoms .
Moreover , in human autoimmune diseases , such as multiple sclerosis @ @ @ @ @ pathogenic role of vitamin D has been described .
The review aims at describing the @ @ @ @ @ D from the cellular level through autoimmune animal models and depicting the known contribution of @ @ @ @ @ of human autoimmune diseases .

Vitamin D, besides having well-known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune-homeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune-regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases.


greenmedinfo--2020-04-23--Vitamin D as an adjunctive therapy in asthma. Part 1: A review of potential mechanisms.

Vitamin D deficiency ( VDD ) is highly prevalent worldwide .
The classical role for vitamin D is to regulate calcium absorption form the gastrointestinal tract and influence bone health .
Recently vitamin D receptors and vitamin D metabolic enzymes have been discovered in numerous sites systemically supporting diverse extra-skeletal roles of vitamin D , for example in asthmatic disease .
Further , VDD and asthma share several common risk factors including high latitude , winter season , industrialization , poor diet , obesity , and dark skin pigmentation .
Vitamin D has been demonstrated to possess potent immunomodulatory effects @ @ @ @ @ @ @ B cells as well as increasing production of antimicrobial peptides ( e.g .
cathelicidin ) .
This immunomodulation may lead to asthma specific clinical benefits in terms of decreased bacterial/viral infections , altered airway smooth muscle-remodeling and -function as well as modulation of response to standard anti-asthma therapy ( e.g .
glucocorticoids and immunotherapy ) .
Thus , vitamin D and its deficiency have a number of biological effects that are potentially important in altering the course of disease pathogenesis and severity in asthma .
The purpose of this first of a two-part @ @ @ @ @ @ @ altering vitamin D status may influence asthmatic disease .

Vitamin D deficiency (VDD) is highly prevalent worldwide. The classical role for vitamin D is to regulate calcium absorption form the gastrointestinal tract and influence bone health. Recently vitamin D receptors and vitamin D metabolic enzymes have been discovered in numerous sites systemically supporting diverse extra-skeletal roles of vitamin D, for example in asthmatic disease. Further, VDD and asthma share several common risk factors including high latitude, winter season, industrialization, poor diet, obesity, and dark skin pigmentation. Vitamin D has been demonstrated to possess potent immunomodulatory effects, including effects on T cells and B cells as well as increasing production of antimicrobial peptides (e.g. cathelicidin). This immunomodulation may lead to asthma specific clinical benefits in terms of decreased bacterial/viral infections, altered airway smooth muscle-remodeling and -function as well as modulation of response to standard anti-asthma therapy (e.g. glucocorticoids and immunotherapy). Thus, vitamin D and its deficiency have a number of biological effects that are potentially important in altering the course of disease pathogenesis and severity in asthma. The purpose of this first of a two-part review is to review potential mechanisms whereby altering vitamin D status may influence asthmatic disease.


greenmedinfo--2020-04-23--The vitamin D-antimicrobial peptide pathway and its role in protection against infection.

Vitamin D deficiency has been correlated with increased rates of infection .
Since the early 19th century , both environmental ( i.e.
, sunlight ) and dietary sources ( cod liver ) of vitamin D have been identified as treatments for TB .
The recent discovery that vitamin D induces antimicrobial peptide gene expression explains , in part , the 'antibiotic ' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function .
Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to @ @ @ @ @ @ @ lead to suboptimal responses toward bacterial and viral infections .
The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals .
The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems .
Future studies in both @ @ @ @ @ @ @ the importance of this regulation and lead to the development of potential therapeutic applications .

Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications.


greenmedinfo--2020-04-23--Mechanisms underlying the effect of vitamin D on the immune system.

Vitamin D and the vitamin D receptor ( VDR ) have been shown to be important regulators of the immune @ @ @ @ @ vitamin D and VDR deficiency exacerbates experimental autoimmune diseases such as inflammatory bowel disease ( @ @ @ @ @ due to an immune-mediated attack by pathogenic T-cells that overproduce IL-17 and IFN-gamma and a @ @ @ @ @ knockout mice have twice as many T-cells making IL-17 and IFN-gamma than wild-type mice .
@ @ @ @ @ and the VDR are required for normal numbers of regulatory T-cells ( iNKT and CD8alphaalpha @ @ @ @ @ to suppress experimental IBD .
In the absence of vitamin D and the VDR , @ @ @ @ @ tract due to increased numbers of IL-17 and IFN-gamma secreting T-cells and a concomitant reduction @ @ @ @

Vitamin D and the vitamin D receptor (VDR) have been shown to be important regulators of the immune system. In particular, vitamin D and VDR deficiency exacerbates experimental autoimmune diseases such as inflammatory bowel disease (IBD). IBD develops due to an immune-mediated attack by pathogenic T-cells that overproduce IL-17 and IFN-gamma and a few regulatory cells. VDR knockout mice have twice as many T-cells making IL-17 and IFN-gamma than wild-type mice. In addition, vitamin D and the VDR are required for normal numbers of regulatory T-cells (iNKT and CD8alphaalpha) that have been shown to suppress experimental IBD. In the absence of vitamin D and the VDR, autoimmunity occurs in the gastrointestinal tract due to increased numbers of IL-17 and IFN-gamma secreting T-cells and a concomitant reduction in regulatory T-cells.


greenmedinfo--2020-04-23--Current status in vitamin D and regulatory T cells--immunological implications.

There has been a continuous effort to understand possible non-Ca metabolism roles of vitamin D , including its role in the immune system and , in particular , in T cell-medicated immunity .
Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations , when we refer to immune system , and pretty much in any human tissue and cells .
Until the eighties , no one had imagined that vitamin D might play a role in the functioning of the immune system .
Today we accepted that the normal immune system harbors a regulatory @ @ @ @ @ @ @ for immune suppression .
Currently , the most commonly known regulatory T-cell lineage is called CD4+ CD25high FoxP3+ regulatory T cells .
Several autoimmune disorders have been linked to a deficiency in vitamin D3 .
In some autoimmune diseases , including multiple sclerosis ( MS ) , a compromised Treg function is believed to be critically involved in the disease process .
Vitamin D insufficiency has ramifications not only for bone health , but also in other non-skeletal areas of vitamin D function , such as immune cells , muscle cells and , @ @ @ @ @ @ @ conclusion , further researches in the field of vitamin D , Tregs , immunity ( inflammatory processes , rejection , autoimmune diseases , etc . )
, either in vitro on cell cultures or in vivo using lab animals or volunteers are still necessary .

There has been a continuous effort to understand possible non-Ca metabolism roles of vitamin D, including its role in the immune system and, in particular, in T cell-medicated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations, when we refer to immune system, and pretty much in any human tissue and cells. Until the eighties, no one had imagined that vitamin D might play a role in the functioning of the immune system. Today we accepted that the normal immune system harbors a regulatory T cell (Treg) population specialized for immune suppression. Currently, the most commonly known regulatory T-cell lineage is called CD4+ CD25high FoxP3+ regulatory T cells. Several autoimmune disorders have been linked to a deficiency in vitamin D3. In some autoimmune diseases, including multiple sclerosis (MS), a compromised Treg function is believed to be critically involved in the disease process. Vitamin D insufficiency has ramifications not only for bone health, but also in other non-skeletal areas of vitamin D function, such as immune cells, muscle cells and, perhaps, adipocytes. As a final conclusion, further researches in the field of vitamin D, Tregs, immunity (inflammatory processes, rejection, autoimmune diseases, etc.), either in vitro on cell cultures or in vivo using lab animals or volunteers are still necessary.


greenmedinfo--2020-04-23--The present study suggests that Vitamin D3 is a potentially useful agent for limiting influenza A vi

The present study suggests that Vitamin D3 is a potentially useful agent for limiting influenza A virus-induced cellular injury via its pro-autophagic action.

Vitamin D3/Calcitriol supplementation in humans is associated with reduced incidence and severity during influenza A virus ( IAV ) infection .
Apoptosis in response to IAV infection is a major contributor to host cell death and tissue damage ; however , its modulation by Vitamin D3 remains unclear .
In this study , we demonstrate the efficacy of Vitamin D3 in preventing apoptosis induction by pandemic influenza A ( H1N1 ) pdm09 virus in human alveolar cells ( A549 ) .
Human alveolar epithelial cell line A549 was used to assess the cytotoxic effects of IAV infection .
Immunoblotting and @ @ @ @ @ @ @ and autophagy .
The results of the present study demonstrate that IAV induces apoptosis by subversion of host autophagy via down-regulating components of autophagic machinery involved in autophagosome-lysosome fusion and lysosomal activity .
Vitamin D3 restores the autophagic flux inhibited by IAV by upregulating the expression of Syntaxin-17 ( STX17 ) and V-type proton ATPase subunit ( ATP6V0A2 ) thereby causing a concomitant decrease in cellular apoptosis via a Vitamin D3 receptor ( VDR ) dependent mechanism .
The present study suggests that Vitamin D3 is a potentially useful agent for limiting IAV-induced @ @ @ @ @ @ @

Vitamin D3/Calcitriol supplementation in humans is associated with reduced incidence and severity during influenza A virus (IAV) infection. Apoptosis in response to IAV infection is a major contributor to host cell death and tissue damage; however, its modulation by Vitamin D3 remains unclear. In this study, we demonstrate the efficacy of Vitamin D3 in preventing apoptosis induction by pandemic influenza A (H1N1)pdm09 virus in human alveolar cells (A549). Human alveolar epithelial cell line A549 was used to assess the cytotoxic effects of IAV infection. Immunoblotting and fluorescence microscopy were used to study apoptosis and autophagy. The results of the present study demonstrate that IAV induces apoptosis by subversion of host autophagy via down-regulating components of autophagic machinery involved in autophagosome-lysosome fusion and lysosomal activity. Vitamin D3 restores the autophagic flux inhibited by IAV by upregulating the expression of Syntaxin-17 (STX17) and V-type proton ATPase subunit (ATP6V0A2) thereby causing a concomitant decrease in cellular apoptosis via a Vitamin D3 receptor (VDR) dependent mechanism. The present study suggests that Vitamin D3 is a potentially useful agent for limiting IAV-induced cellular injury via its pro-autophagic action.


greenmedinfo--2020-04-23--Vitamin D suppresses ovarian cancer growth and invasion by targeting long non-coding RNA CCAT2.

Ovarian cancer is the most deadly gynecologic cancer among women worldwide .
Poor response to current treatment makes it necessary @ @ @ @ @ to detect the cancer early and develop new and effective prevention strategies .
Calcitriol , @ @ @ @ @ D , protects against multiple cancers through unelucidated mechanisms .
The oncogenic long non-coding RNA @ @ @ @ @ colon cancer associated transcript 2 ) is overexpressed in ovarian cancer .
Here , we @ @ @ @ @ expression in ovarian cancer cell lines .
Treatment with calcitriol inhibited ovarian cancer cell proliferation @ @ @ @ @ .
As a result of CCAT2 inhibition , calcitriol decreased the binding of transcription factor @ @ @ @ @ thepromoter , resulting in the repression of c-Myc protein expression .
Our results suggest a @ @ @ @ @ D by targeting CCAT2 in ovarian cancer .
The findings may help develop vitamin D @ @ @ @ @ nutraceutical for ovarian cancer prevention .

Ovarian cancer is the most deadly gynecologic cancer among women worldwide. Poor response to current treatment makes it necessary to discover new diagnostic biomarkers to detect the cancer early and develop new and effective prevention strategies. Calcitriol, the active metabolite of vitamin D, protects against multiple cancers through unelucidated mechanisms. The oncogenic long non-coding RNA (lncRNA) CCAT2 (colon cancer associated transcript 2) is overexpressed in ovarian cancer. Here, we foundd that calcitriol inhibited CCAT2 expression in ovarian cancer cell lines. Treatment with calcitriol inhibited ovarian cancer cell proliferation, migration, and invasion. As a result of CCAT2 inhibition, calcitriol decreased the binding of transcription factor TCF7L2 (TCF4) to thepromoter, resulting in the repression of c-Myc protein expression. Our results suggest a novel anti-cancer mechanism of vitamin D by targeting CCAT2 in ovarian cancer. The findings may help develop vitamin D as a practical and inexpensive nutraceutical for ovarian cancer prevention.


greenmedinfo--2020-04-23--Calcitriol ameliorates kidney injury through reducing podocytopathy, tubular injury, inflammation an

Calcitriol ameliorates kidney injury through reducing podocytopathy, tubular injury, inflammation and fibrosis.

Chronic kidney diseases ( CKDs ) lead to end-stage renal diseases ( ESRD ) which are characterized by glomerulosclerosis , tubular injury , anemia , inflammation , and interstitial fibrosis .
Vitamin D is known to have renal protective effects .
However , its effects relate to low and high doses of Vitamin D in CKD model is still unknown .
CKD was performed using 5/6 subtotal nephrectomy procedure in male Sprague Dawley rats ( 3 months old , 200-300 grams , SN group ; n=6 ) , then rats were sacrificed on day 14 after operation .
Sham operation @ @ @ @ @ @ @ ; n=6 ) .
Calcitriol was administered in two doses : 0.01µg/mL/100 gramsBW/day ( SND1 group ; n=6 ) and 0.05 µg/mL/100 gramsBW/day ( SND2 group ; n=6 ) intraperitoneally for 14 days .
Glomerulosclerosis and tubular injury score were examined using PAS staining , meanwhile , interstitial fibrosis area fraction was assessed with Sirius Red staining .
RT-PCR was performed for assessing nephrin , podocin , IL-6 , CD68 , Collagen-1 , and TGF-β1 mRNA expressions .
Immunostaining ( IHC ) was carried out to observe macrophage ( CD68 ) and myofibroblast @ @ @ @ @ @ @ condition with higher tubular injury , glomerulosclerosis , interstitial fibrosis , and inflammation compared to SO .
Calcitriol-treated group ( especially SND2 ) demonstrated significant lower tubular injury , glomerulosclerosis , and interstitial fibrosis compared to SN .
SND2 group showed not only significantly lower CD68 , IL-6 , Collagen-1 , and TGF-β1 mRNA expressions , but also higher mRNA expressions of nephrin and podocin .
SND2 group also demonstrated reduction of macrophages infiltration and myofibroblasts expansion based on its histopathological appearance .
Vitamin D may have a renoprotective effect on 5/6 subtotal @ @ @ @ @ @ @ injury , inflammation and interstitial fibrosis .

Chronic kidney diseases (CKDs) lead to end-stage renal diseases (ESRD) which are characterized by glomerulosclerosis, tubular injury, anemia, inflammation, and interstitial fibrosis. Vitamin D is known to have renal protective effects. However, its effects relate to low and high doses of Vitamin D in CKD model is still unknown. CKD was performed using 5/6 subtotal nephrectomy procedure in male Sprague Dawley rats (3 months old, 200-300 grams, SN group; n=6), then rats were sacrificed on day 14 after operation. Sham operation was used for control (SO group; n=6). Calcitriol was administered in two doses : 0.01µg/mL/100 gramsBW/day (SND1 group; n=6) and 0.05 µg/mL/100 gramsBW/day (SND2 group; n=6) intraperitoneally for 14 days. Glomerulosclerosis and tubular injury score were examined using PAS staining, meanwhile, interstitial fibrosis area fraction was assessed with Sirius Red staining. RT-PCR was performed for assessing nephrin, podocin, IL-6, CD68, Collagen-1, and TGF-β1 mRNA expressions. Immunostaining (IHC) was carried out to observe macrophage (CD68) and myofibroblast (α-SMA). SN demonstrated CKD condition with higher tubular injury, glomerulosclerosis, interstitial fibrosis, and inflammation compared to SO. Calcitriol-treated group (especially SND2) demonstrated significant lower tubular injury, glomerulosclerosis, and interstitial fibrosis compared to SN. SND2 group showed not only significantly lower CD68, IL-6, Collagen-1, and TGF-β1 mRNA expressions, but also higher mRNA expressions of nephrin and podocin. SND2 group also demonstrated reduction of macrophages infiltration and myofibroblasts expansion based on its histopathological appearance. Vitamin D may have a renoprotective effect on 5/6 subtotal nephrectomy model by attenuating podocytopathy, tubular injury, inflammation and interstitial fibrosis.


greenmedinfo--2020-04-23--Vitamin D and respiratory infection in adults.

Vitamin D insufficiency is a global issue that has significant implications for health .
The classical role of vitamin D in bone mineralisation is well known ; vitamin D deficiency leads to rickets , osteomalacia or osteoporosis .
The role of vitamin D in an immune system is less known .
Vitamin D is not an actual vitamin but a secosteroid hormone produced in the skin from 7-dehydrocholesterol after exposure to sunlight UVB radiation .
Nutrition and supplements are main sources of vitamin D in wintertime in northern countries as sunlight exposure is inadequate for the production .
For activation @ @ @ @ @ @ @ liver to form 25-hydroxyvitamin D and in kidney to 1,25-dihydroxyvitamin D , the most active hormone in Ca absorption in the gut .
For determination of vitamin D status serum 25-hydroxyvitamin D level , the major circulating form of the hormone is to be measured .
Vitamin D regulates gene expression through binding with vitamin D receptors , which dimerises with retinoid X receptor .
This complex binds to vitamin D-responsive elements inside the promoter regions of vitamin D-responsive genes .
Vitamin D has a key role in innate immunity activation ; the @ @ @ @ @ @ @ defensins ) following Toll-like receptor stimulation by pathogen lipopeptides is dependent on sufficient level of 25-hydroxyvitamin D. Clinically , there is evidence of the association of vitamin D insufficiency and respiratory tract infections .
There is also some evidence of the prevention of infections by vitamin D supplementation .
Randomised controlled trials are warranted to explore this preventive effect .

Vitamin D insufficiency is a global issue that has significant implications for health. The classical role of vitamin D in bone mineralisation is well known; vitamin D deficiency leads to rickets, osteomalacia or osteoporosis. The role of vitamin D in an immune system is less known. Vitamin D is not an actual vitamin but a secosteroid hormone produced in the skin from 7-dehydrocholesterol after exposure to sunlight UVB radiation. Nutrition and supplements are main sources of vitamin D in wintertime in northern countries as sunlight exposure is inadequate for the production. For activation vitamin D needs to be hydroxylated in liver to form 25-hydroxyvitamin D and in kidney to 1,25-dihydroxyvitamin D, the most active hormone in Ca absorption in the gut. For determination of vitamin D status serum 25-hydroxyvitamin D level, the major circulating form of the hormone is to be measured. Vitamin D regulates gene expression through binding with vitamin D receptors, which dimerises with retinoid X receptor. This complex binds to vitamin D-responsive elements inside the promoter regions of vitamin D-responsive genes. Vitamin D has a key role in innate immunity activation; the production of antimicrobial peptides (cathelicidin and defensins) following Toll-like receptor stimulation by pathogen lipopeptides is dependent on sufficient level of 25-hydroxyvitamin D. Clinically, there is evidence of the association of vitamin D insufficiency and respiratory tract infections. There is also some evidence of the prevention of infections by vitamin D supplementation. Randomised controlled trials are warranted to explore this preventive effect.


greenmedinfo--2020-04-23--Vitamin D endocrine system involvement in autoimmune rheumatic diseases.

Vitamin D is synthesized from cholesterol in the skin ( 80-90 % ) under the sunlight and then metabolized into an active D hormone in liver , kidney and peripheral immune/inflammatory cells .
These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme , 1alpha-hydroxylase ( CYP27B1 ) , and the vitamin D receptor ( VDR ) on cells of the immune system in mediating intracrine and paracrine actions .
Vitamin D is implicated in prevention and protection from chronic infections ( i.e .
tubercolosis ) , cancer ( i.e .
breast cancer ) and autoimmune rheumatic @ @ @ @ @ @ @ immunity potentiating the innate response ( monocytes/macrophages with antimicrobial activity and antigen presentation ) , but suppressing the adaptive immunity ( T and B lymphocyte functions ) .
Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25 ( OH ) 2D3 does indeed exert direct effects on B cell homeostasis .
A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus .
Recently , @ @ @ @ @ @ @ during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels .

Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels.


greenmedinfo--2020-04-23--Vitamin D and lung disease.

Vitamin D and lung disease.

The classic role of vitamin D in the regulation of calcium and phosphate metabolism , and its effects on bone @ @ @ @ @ .
More recently a critical role in immunity and respiratory health has been proposed .
@ @ @ @ @ the capacity to generate the active metabolite , 1α,25-dihydroxyvitamin D3 ( 1,25 ( OH ) @ @ @ @ @ many tissues beyond the kidney ; expression of the vitamin D receptor ( VDR ) @ @ @ @ @ not involved in calcium-phosphate homeostasis ; and control by 1,25 ( OH ) D3 of @ @ @ @ @ with numerous different biological processes through its nuclear VDR .
Abnormalities in the vitamin D @ @ @ @ @ prevalence of vitamin D insufficiency worldwide , now appear important in a wide range of @ @ @ @ @ bacterial respiratory infection , asthma , chronic obstructive pulmonary disease , and cancer .
Actions @ @ @ @ @ immune responses , for example , production of antimicrobial peptides and autophagy , and on @ @ @ @ @ example , promoting regulatory lymphocytes , are believed to underpin these associations .

The classic role of vitamin D in the regulation of calcium and phosphate metabolism, and its effects on bone health, are well established. More recently a critical role in immunity and respiratory health has been proposed. This arises from evidence for the capacity to generate the active metabolite, 1α,25-dihydroxyvitamin D3 (1,25(OH)D3), locally in many tissues beyond the kidney; expression of the vitamin D receptor (VDR) in immune and structural cells not involved in calcium-phosphate homeostasis; and control by 1,25(OH)D3 of the transcription of genes associated with numerous different biological processes through its nuclear VDR. Abnormalities in the vitamin D axis, including a high prevalence of vitamin D insufficiency worldwide, now appear important in a wide range of pulmonary diseases including viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. Actions of vitamin D on innate immune responses, for example, production of antimicrobial peptides and autophagy, and on adaptive immune responses, for example, promoting regulatory lymphocytes, are believed to underpin these associations.


greenmedinfo--2020-04-23--The molecular and clinical evidence of vitamin D signaling as a modulator of the immune system: Role

The molecular and clinical evidence of vitamin D signaling as a modulator of the immune system: Role in Behçet's disease.

Various tissues and cell types are the targets of vitamin D. However , the major targets of vitamin D in @ @ @ @ @ , dendritic cells ( DCs ) , as well as B and T cells .
@ @ @ @ @ role in the immune system modulation via regulating the expression of genes that generate pro-inflammatory @ @ @ @ @ of pro-inflammatory cells , both of which have been implicated in the pathophysiology of the @ @ @ @ @ have revealed the important relations between vitamin D and Behçet 's disease ( BD ) @ @ @ @ @ its deficiency have been linked to a wide range of metabolic disorders including malignant , @ @ @ @ @ , and autoimmune diseases .
Here , we provide a brief analysis of the recent @ @ @ @ @ well as clinical evidence of vitamin D influence on the molecular level in BD .

Various tissues and cell types are the targets of vitamin D. However, the major targets of vitamin D in the immune system are monocytes/macrophages, dendritic cells (DCs), as well as B and T cells. Vitamin D plays an important role in the immune system modulation via regulating the expression of genes that generate pro-inflammatory mediators and inhibiting the proliferation of pro-inflammatory cells, both of which have been implicated in the pathophysiology of the inflammatory diseases. Recent studies have revealed the important relations between vitamin D and Behçet's disease (BD). Vitamin D function and its deficiency have been linked to a wide range of metabolic disorders including malignant, cardiovascular, infectious, neuromuscular, and autoimmune diseases. Here, we provide a brief analysis of the recent literature regarding immune-regulatory effects as well as clinical evidence of vitamin D influence on the molecular level in BD.


greenmedinfo--2020-04-23--Vitamin effects on the immune system: vitamins A and D take centre stage.

Vitamins are essential constituents of our diet that have long been known to influence the immune system .
Vitamins A @ @ @ @ @ attention in recent years as these vitamins have been shown to have an unexpected and @ @ @ @ @ response .
We present and discuss our current understanding of the essential roles of vitamins @ @ @ @ @ of immune processes , such as lymphocyte activation and proliferation , T-helper-cell differentiation , tissue-specific @ @ @ @ @ of specific antibody isotypes and regulation of the immune response .
Finally , we discuss @ @ @ @ @ A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation @ @ @

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.


greenmedinfo--2020-04-22--Vitamin D and innate and adaptive immunity.

In the last 5 years there has been renewed interest in the health benefits of vitamin D. A central feature of this revival has been new information concerning the nonclassical effects of vitamin D. In particular , studies of the interaction between vitamin D and the immune system have highlighted the importance of localized conversion of precursor 25-hydroxyvitamin D ( 25OHD ) to active 1,25-dihydroxyvitamin D ( 1,25 ( OH ) ( 2 ) D ) as a mechanism for maintaining antibacterial activity in humans .
The clinical relevance of this has been endorsed by increasing evidence of suboptimal 25OHD @ @ @ @ @ @ @ Collectively these observations support the hypothesis that vitamin D insufficiency may lead to dysregulation of human immune responses and may therefore be an underlying cause of infectious disease and immune disorders .
The current review describes the key mechanisms associated with vitamin D metabolism and signaling for both innate immune ( antimicrobial activity and antigen presentation ) and adaptive immune ( T and B lymphocyte function ) responses .
These include coordinated actions of the vitamin D-activating enzyme , 1α-hydroxylase ( CYP27B1 ) , and the vitamin D receptor ( VDR ) in @ @ @ @ @ @ @ D. Finally , the review will consider the role of immunomodulatory vitamin D in human health , with specific emphasis on infectious and autoimmune disease .

In the last 5 years there has been renewed interest in the health benefits of vitamin D. A central feature of this revival has been new information concerning the nonclassical effects of vitamin D. In particular, studies of the interaction between vitamin D and the immune system have highlighted the importance of localized conversion of precursor 25-hydroxyvitamin D (25OHD) to active 1,25-dihydroxyvitamin D (1,25(OH)(2)D) as a mechanism for maintaining antibacterial activity in humans. The clinical relevance of this has been endorsed by increasing evidence of suboptimal 25OHD status in populations across the globe. Collectively these observations support the hypothesis that vitamin D insufficiency may lead to dysregulation of human immune responses and may therefore be an underlying cause of infectious disease and immune disorders. The current review describes the key mechanisms associated with vitamin D metabolism and signaling for both innate immune (antimicrobial activity and antigen presentation) and adaptive immune (T and B lymphocyte function) responses. These include coordinated actions of the vitamin D-activating enzyme, 1α-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) in mediating intracrine and paracrine actions of vitamin D. Finally, the review will consider the role of immunomodulatory vitamin D in human health, with specific emphasis on infectious and autoimmune disease.


greenmedinfo--2020-04-22--Geraniol attenuates oxidative stress, bioaccumulation, serological and histopathological changes dur

Geraniol attenuates oxidative stress, bioaccumulation, serological and histopathological changes during aluminum chloride-hepatopancreatic toxicity in male rats.

Aluminum chloride ( AlCl ) has different industrial applications including manufacturing paint and water treatment .
The present study was @ @ @ @ @ effect of geraniol against AlCl-induced hepatopancreatic toxicity .
To this end , forty male Wistar @ @ @ @ @ ( 0.9 % NaCl , IP ) , geraniol ( 100 mg/kg orally ) , @ @ @ @ @ IP ) , and AlCl ( 70 mg/kg , IP ) plus geraniol ( 100 @ @ @ @ @ then were treated daily for 28 days .
Based on the results , serum cholesterol @ @ @ @ @ as liver and pancreas enzymes increased significantly ( P

Aluminum chloride (AlCl) has different industrial applications including manufacturing paint and water treatment. The present study was designed to evaluate the alleviating effect of geraniol against AlCl-induced hepatopancreatic toxicity. To this end, forty male Wistar rats were divided into control (0.9% NaCl, IP), geraniol (100 mg/kg orally), AlCl(70 mg/kg, IP), and AlCl(70 mg/kg, IP) plus geraniol (100 mg/kg orally) groups and then were treated daily for 28 days. Based on the results, serum cholesterol, triglyceride, as well as liver and pancreas enzymes increased significantly (P < 0.05) while the level of insulin significantly decreased in AlCl-treated rats compared to the control group (P < 0.05). The presence of geraniol relieved the toxic effects of AlClas well. On the other hand, the level of malondialdehyde (MDA) increased in the AlCl-treated group while the activities of glutathione peroxidase and the total antioxidant activity demonstrated a reduction. However, the MDA level decreased while the antioxidant enzymes increased in co-treated with geraniol group. Histopathological examination revealed that simultaneous treatment with geraniol in AlClintoxicated rats ameliorate the liver lesions such as necrosis, inflammatory cell infiltration, vacuolar degeneration, along with hyperemia and the cell density of the Langerhans islands. Finally, the results indicated that geraniol attenuated the side effect of AlCl-induced hepatopancreatic toxicity.


greenmedinfo--2020-04-22--Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shige

Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis.

BACKGROUND : Several studies showed benefits of long-term zinc supplementation on the incidence , severity , and duration of diarrhea and on the incidence of respiratory infections .
Prolonged zinc supplementation also improves cell-mediated immunity in severely malnourished children .
OBJECTIVE : We studied the effect of short-term zinc supplementation on intrinsic and specific immune and inflammatory responses in moderately malnourished children with acute shigellosis .
DESIGN : A randomized , double-blind , placebo-controlled trial was conducted in Shigella-infected children aged 12-59 mo .
Elemental zinc ( 20 mg ) and a multivitamin containing vitamins A and D , thiamine @ @ @ @ @ @ @ at twice the recommended dietary allowance were given daily for 2 wk to the zinc group ( n = 28 ) , whereas the multivitamin alone was given to the control group ( n = 28 ) .
Standard antibiotic therapy was given to all patients .
RESULTS : Serum zinc concentrations increased in both groups during convalescence ; however , zinc supplementation showed a significant effect .
The lymphocyte proliferation response in the zinc group increased relative to that in the control group ( P = 0.002 ) , but no significant @ @ @ @ @ @ @ ( interleukin 2 and interferon gamma ) released from mitogen-stimulated mononuclear cells or on concentrations of cytokines ( interleukin 2 , interferon gamma , and interleukin 1beta ) in feces .
Among the antigen [ lipopolysaccharide and invasion plasmid-encoded antigen ( Ipa ) ] -specific antibodies , plasma Ipa-specific immunoglobulin G responses at day 30 were significantly higher in the zinc group than in the control group .
However , the 2 groups did not differ significantly in the other antigen-specific responses in plasma and stool .
CONCLUSION : A 14-d course of @ @ @ @ @ @ @ lymphocyte proliferation response and the Ipa-specific immunoglobulin G response .

BACKGROUND: Several studies showed benefits of long-term zinc supplementation on the incidence, severity, and duration of diarrhea and on the incidence of respiratory infections. Prolonged zinc supplementation also improves cell-mediated immunity in severely malnourished children.
OBJECTIVE: We studied the effect of short-term zinc supplementation on intrinsic and specific immune and inflammatory responses in moderately malnourished children with acute shigellosis.
DESIGN: A randomized, double-blind, placebo-controlled trial was conducted in Shigella-infected children aged 12-59 mo. Elemental zinc (20 mg) and a multivitamin containing vitamins A and D, thiamine, riboflavin, nicotinamide, and calcium at twice the recommended dietary allowance were given daily for 2 wk to the zinc group (n = 28), whereas the multivitamin alone was given to the control group (n = 28). Standard antibiotic therapy was given to all patients.
RESULTS: Serum zinc concentrations increased in both groups during convalescence; however, zinc supplementation showed a significant effect. The lymphocyte proliferation response in the zinc group increased relative to that in the control group (P = 0.002), but no significant effects were seen on concentrations of cytokines (interleukin 2 and interferon gamma) released from mitogen-stimulated mononuclear cells or on concentrations of cytokines (interleukin 2, interferon gamma, and interleukin 1beta) in feces. Among the antigen [lipopolysaccharide and invasion plasmid-encoded antigen (Ipa)]-specific antibodies, plasma Ipa-specific immunoglobulin G responses at day 30 were significantly higher in the zinc group than in the control group. However, the 2 groups did not differ significantly in the other antigen-specific responses in plasma and stool.
CONCLUSION: A 14-d course of zinc supplementation during acute shigellosis increases the lymphocyte proliferation response and the Ipa-specific immunoglobulin G response.


greenmedinfo--2020-04-22--Topical riboflavin attenuates ultraviolet B- and ultraviolet A-induced immunosuppression in humans.

BACKGROUND : Riboflavin ( vitamin B ( 2 ) ) plays a key role in cellular energy metabolism .
We have observed previously that nicotinamide ( vitamin B ( 3 ) ) , which is also centrally involved in cellular energy restoration after UV irradiation , is highly immune protective in humans .
We thus hypothesized that riboflavin might also confer immune protection .
METHODS : We irradiated healthy , nickel-allergic volunteers with narrowband UVA ( 385 nm ) and UVB ( 300 nm ) at separate sites on the lower back .
These areas were treated with riboflavin solution @ @ @ @ @ @ @ at 30 min before UV exposure .
Forty-eight hours after irradiation , volunteers were patch tested with nickel-containing Finn chambers , at both irradiated and nonirradiated sites , with and without prior riboflavin treatment .
The resulting contact hypersensitivity reactions at each site were then measured 72 h later with a reflectance erythema meter in order to determine and compare the immune suppressive effects of each intervention .
RESULTS : We observed that low doses of both UVB and longwave UVA1 were immune suppressive in humans .
Topical riboflavin conferred immune protection against @ @ @ @ @ @ @ immune protective in humans , and this may reflect the role of the B group vitamins in cellular energy restoration after UV exposure .

BACKGROUND: Riboflavin (vitamin B(2)) plays a key role in cellular energy metabolism. We have observed previously that nicotinamide (vitamin B(3)), which is also centrally involved in cellular energy restoration after UV irradiation, is highly immune protective in humans. We thus hypothesized that riboflavin might also confer immune protection.
METHODS: We irradiated healthy, nickel-allergic volunteers with narrowband UVA (385 nm) and UVB (300 nm) at separate sites on the lower back. These areas were treated with riboflavin solution or vehicle at 24 h and again at 30 min before UV exposure. Forty-eight hours after irradiation, volunteers were patch tested with nickel-containing Finn chambers, at both irradiated and nonirradiated sites, with and without prior riboflavin treatment. The resulting contact hypersensitivity reactions at each site were then measured 72 h later with a reflectance erythema meter in order to determine and compare the immune suppressive effects of each intervention.
RESULTS: We observed that low doses of both UVB and longwave UVA1 were immune suppressive in humans. Topical riboflavin conferred immune protection against both wavebands.
CONCLUSIONS: Riboflavin is immune protective in humans, and this may reflect the role of the B group vitamins in cellular energy restoration after UV exposure.