The role of vitamin D in malaria.

An abnormal calcium-parathyroid hormone (PTH)-vitamin D axis has been reported in patients with malaria infection. A role for vitamin D in malaria has been suggested by many studies. Genetic studies have identified numerous factors that link vitamin D to malaria, including human leukocyte antigen genes, toll-like receptors, heme oxygenase-1, angiopoietin-2, cytotoxic T lymphocyte antigen-4, nucleotide-binding oligomerization domain-like receptors, and Bcl-2. Vitamin D has also been implicated in malaria via its effects on the Bacillus Calmette-Guerin (BCG) vaccine, matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, reactive oxidative species, and nitric oxide synthase. Vitamin D may be important in malaria; therefore, additional research on its role in malaria is needed.

The role of vitamin d in autoimmune hepatitis.

Autoimmune hepatitis is an inflammation of the liver characterized by the presence of peri-portal hepatitis, hypergammaglobulinemia, and the serum autoantibodies. The disease is classified into 2 distinct types according to the nature of auto-antibodies. Disturbances of the calcium-parathyroid hormone-vitamin D axis are frequently associated with chronic liver disease. Patients with AIH have a high prevalence of vitamin D deficiency. Genetic studies have provided the opportunity to determine which proteins link vitamin D to AIH pathology, namely, the major histocompatibility complex class II molecules, vitamin D receptors, toll-like receptors, cytotoxic T lymphocyte antigen-4, cytochrome P450 CYP2D6, regulatory T cells (Tregs) and the forkhead/winged helix transcription factor 3. Vitamin D also exerts its effect on AIH through non-genomic factors, namely, mitogen-activated protein kinase signaling pathways, γδT cells, interferon-gamma nitric oxide synthase, and reactive oxygen stress. In conclusion, vitamin D may have a beneficial role in AIH and improves liver function in concanavalin A-induced mouse AIH. Calcitriol is best used for AIH because it is the active form of a vitamin D3 metabolite and its receptors are present in sinusoidal endothelial cells, Kupffer cells, stellate cells of normal livers, and the biliary cell line.

Beneficial role of vitamin D3 in the prevention of certain respiratory diseases.

There is evidence of aberrations in the vitamin D-endocrine system in subjects with respiratory diseases. Vitamin D deficiency is highly prevalent in patients with respiratory diseases, and patients who receive vitamin D have significantly larger improvements in inspiratory muscle strength and maximal oxygen uptake. Studies have provided an opportunity to determine which proteins link vitamin D to respiratory pathology, including the major histocompatibility complex class II molecules, vitamin D receptor, vitamin D-binding protein, chromosome P450, Toll-like receptors, poly(ADP-ribose) polymerase-1, and the reduced form of nicotinamide adenine dinucleotide phosphate. Vitamin D also exerts its effect on respiratory diseases through cell signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the Wnt/ß-catenin signaling pathway, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D plays a significant role in respiratory diseases. The best form of vitamin D for use in the treatment of respiratory diseases is calcitriol because it is the active metabolite of vitamin D3 and modulates inflammatory cytokine expression. Further investigation of calcitriol in respiratory diseases is needed.

The role of thiamine in cancer: possible genetic and cellular signaling mechanisms.

The relationship between supplemental vitamins and various types of cancer has been the focus of recent investigation, and supplemental vitamins have been reported to modulate cancer rates. A significant association has been demonstrated between cancer and low levels of thiamine in the serum. Genetic studies have helped identify a number of factors that link thiamine to cancer, including the solute carrier transporter (SLC19) gene, transketolase, transcription factor p53, poly(ADP-ribose) polymerase-1 gene, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thiamine supplementation may contribute to a high rate of tumor cell survival, proliferation and chemotherapy resistance. Thiamine has also been implicated in cancer through its effects on matrix metalloproteinases, prostaglandins, cyclooxygenase-2, reactive oxygen species, and nitric oxide synthase. However, some studies have suggested that thiamine may exhibit some antitumor effects. The role of thiamine in cancer is controversial. However, thiamine deficiency may occur in patients with cancer and cause serious disorders, including Wernicke's encephalopathy, that require parenteral thiamine supplementation. A very high dose of thiamine produces a growth-inhibitory effect in cancer. Therefore, further investigations of thiamine in cancer are needed to clarify this relationship.

The beneficial role of vitamin D in obesity: possible genetic and cell signaling mechanisms.

The prevalence rates of overweight and obesity are considered an important public issue in the United States, and both of these conditions are increasing among both children and adults. There is evidence of aberrations in the vitamin D-endocrine system in obese subjects. Vitamin D deficiency is highly prevalent in patients with obesity, and many studies have demonstrated the significant effect of calcitriol on adipocytes. Genetic studies have provided an opportunity to determine which proteins link vitamin D to obesity pathology, including the vitamin D receptor, toll-like receptors, the renin-angiotensin system, apolipoprotein E, vascular endothelial growth factor, and poly (ADP-ribose) polymerase-1. Vitamin D also exerts its effect on obesity through cell-signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the reduced form of nicotinamide adenine dinucleotide phosphate, prostaglandins, reactive oxygen species, and nitric oxide synthase.In conclusion, vitamin D may have a role in obesity. The best form of vitamin D for use in the obese individuals is calcitriol because it is the active form of the vitamin D3 metabolite, its receptors are present in adipocytes, and modulates inflammatory cytokine expression.

The role of ß-adrenergic blockers in Parkinson's disease: possible genetic and cell-signaling mechanisms.

Genetic studies have identified numerous factors linking ß-adrenergic blockade to Parkinson's disease (PD), including human leukocyte antigen genes, the renin-angiotensin system, poly(adenosine diphosphate-ribose) polymerase 1, nerve growth factor, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate. ß-Adrenergic blockade has also been implicated in PD via its effects on matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase 2, and nitric oxide synthase. ß-Adrenergic blockade may have a significant role in PD; therefore, the characterization of ß-adrenergic blockade in patients with PD is needed.

The role of Beta-adrenergic receptor blockers in Alzheimer's disease: potential genetic and cellular signaling mechanisms.

According to genetic studies, Alzheimer's disease (AD) is linked to beta-adrenergic receptor blockade through numerous factors, including human leukocyte antigen genes, the renin-angiotensin system, poly(adenosine diphosphate-ribose) polymerase 1, nerve growth factor, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate. Beta-adrenergic receptor blockade is also implicated in AD due to its effects on matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, and nitric oxide synthase. Beta-adrenergic receptor blockade may also have a significant role in AD, although the role is controversial. Behavioral symptoms, sex, or genetic factors, including Beta 2-adrenergic receptor variants, apolipoprotein E, and cytochrome P450 CYP2D6, may contribute to beta-adrenergic receptor blockade modulation in AD. Thus, the characterization of beta-adrenergic receptor blockade in patients with AD is needed.

The role of vitamin d in primary biliary cirrhosis: possible genetic and cell signaling mechanisms.

Primary biliary cirrhosis (PBC) is an immune-mediated chronic inflammatory disease of the liver of unknown etiology. Vitamin D deficiency is highly prevalent in patients with PBC, and many studies have demonstrated the significant effect of calcitriol on liver cell physiology. Vitamin D has antiproliferative and antifibrotic effects on liver fibrosis. Genetic studies have provided an opportunity to determine which proteins link vitamin D to PBC pathology (e.g., the major histocompatibility complex class II molecules, the vitamin D receptor, toll-like receptors, apolipoprotein E, Nramp1, and cytotoxic T lymphocyte antigen-4). Vitamin D also exerts its effect on PBC through cell signaling mechanisms, that is, matrix metalloproteinases, prostaglandins, reactive oxygen species, and the transforming growth factor betas. In conclusion, vitamin D may have a beneficial role in the treatment of PBC. The best form of vitamin D for use in the PBC is calcitriol because it is the active form of vitamin D3 metabolite, and its receptors are present in the sinusoidal endothelial cells, Kupffer cells, and stellate cells of normal livers, as well as in the biliary cell line.

Roles of vitamin D in amyotrophic lateral sclerosis: possible genetic and cellular signaling mechanisms.

Evidence suggests that there are aberrations in the vitamin D-endocrine system in subjects with amyotrophic lateral sclerosis (ALS). Here, we review the relationship between vitamin D and ALS. Vitamin D deficiency was reported in patients with ALS. Dietary vitamin D(3) supplementation improves functional capacity in the G93A transgenic mouse model of ALS. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to ALS pathology, including major histocompatibility complex (MHC) class II molecules, toll-like receptors, poly(ADP-ribose) polymerase-1, heme oxygenase-1, and calcium-binding proteins, as well as the reduced form of nicotinamide adenine dinucleotide phosphate. Vitamin D also exerts its effect on ALS through cell-signaling mechanisms, including glutamate, matrix metalloproteinases, mitogen-activated protein kinase pathways, the Wnt/ß-catenin signaling pathway, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D may have a role in ALS. Further investigation of vitamin D in ALS patients is needed.

The role of thiamine in HIV infection.

Patients infected with HIV have a high prevalence of thiamine deficiency. Genetic studies have provided the opportunity to determine which proteins link thiamine to HIV pathology, i.e., renin-angiotensin system, poly(ADP-ribosyl) polymerase 1, Sp1 promoter gene, transcription factor p53, apoptotic factor caspase 3, and glycogen synthetase kinase 3ß. Thiamine also affects HIV through non-genomic factors, i.e., matrix metalloproteinase, vascular endothelial growth factor, heme oxygenase 1, the prostaglandins, cyclooxygenase 2, reactive oxygen species, and nitric oxide. In conclusion, thiamine may benefit HIV patients, but further investigation of the role of thiamine in HIV infection is needed.

The role of vitamin D in Alzheimer's disease: possible genetic and cell signaling mechanisms.

Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals and is associated with progressive memory loss and cognitive dysfunction. A significant association between AD and low levels of vitamin D has been demonstrated. Furthermore, vitamin D supplements appear to have a beneficial clinical effect on AD by regulating micro-RNA, enhancing toll-like receptors, modulating vascular endothelial factor expression, modulating angiogenin, and advanced glycation end products. Vitamin D also exerts its effects on AD by regulating calcium-sensing receptor expression, enhancing amyloid-ß peptides clearance, interleukin 10, downregulating matrix metalloproteinases, upregulating heme oxygenase 1, and suppressing the reduced form of nicotinamide adenine dinucleotide phosphate expression. In conclusion, vitamin D may play a beneficial role in AD. Calcitriol is the best vitamin D supplement for AD, because it is the active form of the vitamin D3 metabolite and modulates inflammatory cytokine expression. Therefore, further investigation of the role of calcitriol in AD is needed.

Theoretical basis of a beneficial role for vitamin D in viral hepatitis.

Abnormal bone metabolism and dysfunction of the calcium-parathyroid hormone-vitamin D axis have been reported in patients with viral hepatitis. Some studies suggested a relationship between vitamin D and viral hepatitis. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to the pathology of viral hepatitis (i.e., the major histocompatibility complex class II molecules, the vitamin D receptor, cytochrome P450, the renin-angiotensin system, apolipoprotein E, liver X receptor, toll-like receptor, and the proteins regulated by the Sp1 promoter gene). Vitamin D also exerts its effects on viral hepatitis via non-genomic factors, i.e., matrix metalloproteinase, endothelial vascular growth factor, prostaglandins, cyclooxygenase-2, and oxidative stress. In conclusion, vitamin D could have a beneficial role in viral hepatitis. Calcitriol is best used for viral hepatitis because it is the active form of the vitamin D3 metabolite.

The beneficial role of vitamin D in systemic lupus erythematosus (SLE).

Patients with systemic lupus erythematosus (SLE) have a high prevalence of abnormal bone metabolism and vitamin D deficiency. Genetic studies have provided the opportunity to determine the specific proteins linking vitamin D to SLE pathology [i.e., major histocompatibility complex (MHC) class II molecules, the vitamin D receptor (VDR), microRNAs (miRNAs), the renin-angiotensin system (RAS), apolipoprotein E (ApoE), liver X receptor (LXR), and toll-like receptors (TLRs)]. Vitamin D also exerts protective effects against SLE through non-genomic factors, such as ultraviolet radiation (UV) exposure, matrix metalloproteinase (MMPs), heme oxygenase-1 (HO-1), the prostaglandins (PGs), cyclooxygenase-2 (COX-2), and oxidative stress. Thus, vitamin D may play a beneficial role in SLE. Moreover, the use of calcitriol or 1α,25-dihydroxyvitamin D(3) is optimal for the treatment of SLE patients because this active form of the vitamin D(3) metabolite can modulate inflammatory cytokine production. However, further investigation into the effects of calcitriol with SLE is warranted.

The impact of thiamine treatment in the diabetes mellitus.

Thiamine acts as a coenzyme for transketolase (Tk) and for the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism. The relationship between thiamine and diabetes mellitus (DM) has been reported in the literature. Thiamine levels and thiamine-dependent enzyme activities have been reduced in DM. Genetic studies provide opportunity to link the relationship between thiamine and DM (such as Tk, SLC19A2 gene, transcription factor Sp1, α-1-antitrypsin, and p53). Thiamine and its derivatives have been demonstrated to prevent the activation of the biochemical pathways (increased flux through the polyol pathway, formation of advanced glycation end-products, activation of protein kinase C, and increased flux through the hexosamine biosynthesis pathway) induced by hyperglycemia in DM.Thiamine definitively has a role in the diabetic endothelial vascular diseases (micro and macroangiopathy), lipid profile, retinopathy, nephropathy, cardiopathy, and neuropathy.

The role of vitamin D in asthma.

Vitamin D metabolites are important immune-modulatory hormones and are able to suppress Th2-mediated allergic airway disease. Some genetic factors that may contribute to asthma are regulated by vitamin D, such as vitamin D receptor (VDR), human leukocyte antigen genes (HLA), human Toll-like receptors (TLR), matrix metalloproteinases (MMPs), a disintegrin and metalloprotein-33 (ADAM-33), and poly(ADP-ribosyl) polymerase- 1 (PARP-1). Vitamin D has also been implicated in asthma through its effects on the obesity, bacillus Calmettee Guérin (BCG) vaccination and high vitamin D level, vitamin D supplement, checkpoint protein kinase 1 (Chk1), plasminogen activator inhibitor-1 (PAI-1) and gamma delta T cells (gdT). Vitamin D plays a role in asthma and exerts its action through either genomic and/or non-genomic ways.

Thiamine and Parkinson's disease.

Parkinson's disease (PD) is the second most common form of neurodegeneration in the elderly population. PD is clinically characterized by tremors, rigidity, slowness of movement and postural imbalance. A significant association has been demonstrated between PD and low levels of thiamine in the serum, which suggests that elevated thiamine levels might provide protection against PD. Genetic studies have helped identify a number of factors that link thiamine to PD pathology, including the DJ-1 gene, excitatory amino acid transporters (EAATs), the α-ketoglutarate dehydrogenase complex (KGDHC), coenzyme Q10 (CoQ10 or ubiquinone), lipoamide dehydrogenase (LAD), chromosome 7, transcription factor p53, the renin-angiotensin system (RAS), heme oxygenase-1 (HO-1), and poly(ADP-ribose) polymerase-1 gene (PARP-1). Thiamine has also been implicated in PD through its effects on L-type voltage-sensitive calcium channels (L-VSCC), matrix metalloproteinases (MMPs), prostaglandins (PGs), cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), and nitric oxide synthase (NOS). Recent studies highlight a possible relationship between thiamine and PD. Genetic studies provide opportunities to determine which proteins may link thiamine to PD pathology. Thiamine can also act through a number of non-genomic mechanisms that include protein expression, oxidative stress, inflammation, and cellular metabolism. Further studies are needed to determine the benefits of using thiamine as a treatment for PD.

The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: possible genetic and cell-signaling mechanisms.

Cancer is the leading cause of death in the USA, and the incidence of cancer increases dramatically with age. Beta-adrenergic blockers appear to have a beneficial clinical effect in cancer patients. In this paper, we review the evidence of an association between ß-adrenergic blockade and cancer. Genetic studies have provided the opportunity to determine which proteins link ß-adrenergic blockade to cancer pathology. In particular, this link involves the major histocompatibility complex class II molecules, the renin-angiotensin system, transcription factor nuclear factor-kappa-light-chain-enhancer of activated B cells, poly(ADP-ribose) polymerase-1, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate oxidase. Beta-adrenergic blockers also exert anticancer effects through non-genomic factors, including matrix metalloproteinase, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, oxidative stress, and nitric oxide synthase. In conclusion, ß-adrenergic blockade may play a beneficial role in cancer treatment. Additional investigations that examine ß-adrenergic blockers as cancer therapeutics are required to further elucidate this role.

Role of the vitamin D in leprosy.

There is an evidence of abnormal metabolism in the vitamin D endocrine system of patients with leprosy. Bone deformities usually occur in patients with leprosy. Genetic factors, such as the vitamin D receptor, the major histocompatibility complex region, chromosome 20, human toll-like receptors, the natural resistance-associated macrophage protein 1, the nucleotide-binding oligomerization domain containing 2, phosphate-regulating gene with homologies to endopeptidase on the X chromosome and the tyrosine kinase growth factor receptor-ErbB-2, contribute to both vitamin D status and leprosy. The role of vitamin D in leprosy has been demonstrated by its effects on Bacillus Calmette-Guérin vaccination, vascular endothelial growth factor, prostaglandins, reactive oxygen species, reactive nitrogen intermediates, matrix metalloproteinases, antiphospholipid syndrome and the nerve growth factor. Vitamin D plays a definite role in leprosy. Vitamin D, itself, may effect on leprosy through the vitamin D receptors or may influence leprosy through indirect effects.

The beneficial role of vitamin D in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals and is associated with progressive neurodegeneration of the human neocortex. Patients with AD have a high prevalence of vitamin D deficiency, which is also associated with low mood and impaired cognitive performance in older people. Genetic studies have provided the opportunity to determine which proteins link vitamin D to AD pathology (ie, the major histocompatibility complex class II molecules, vitamin D receptor, renin-angiotensin system, apolipoprotein E, liver X receptor, Sp1 promoter gene, and the poly(ADP-ribose) polymerase-1 gene). Vitamin D also exerts its effect on AD through nongenomic factors, that is, L-type voltage-sensitive calcium channels, nerve growth factor, the prostaglandins, cyclooxygenase 2, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D clearly has a beneficial role in AD and improves cognitive function in some patients with AD. Calcitriol, 1 α,25-dihydroxyvitamin D3, is best used for AD because of its active form of vitamin D(3) metabolite and its receptor in the central nervous system.

Impact of vitamin D in the treatment of tuberculosis.

Tuberculosis (TB) is a major global health problem and often coincides with nutritional deficiency. In fact, vitamin D deficiency has been reported among TB patients, and vitamin D receptor polymorphisms are associated with susceptibility to Mycobacterium tuberculosis. High doses of vitamin D were widely used to treat TB patients in the preantibiotic era. This approach was successful: vitamin D can suppress intracellular growth of M tuberculosis in vitro. Vitamin D also induced the expression of cathelicidin, which is involved in the first line of defense in TB patients. Thus, vitamin D may have a role in TB treatment, and further investigation is needed.