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| Pleiotropic effects | Mechanism | Associated diseases |
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| Anti-inflammation | (1) affects the differentiation of active CD4+ T-cells
(2) enhances the inhibitory function of T-cells
(3) promotes differentiation of monocyte into mature macrophages by inducing p21
(4) induces C/EBPβ which contribute to the monocyte-macrophage lineage differentiation, increase the activity of macrophages, and promote their antibacterial and antiviral activities
(5) inhibits the synthesis of IL-12, γ-interferon, and Th1 immune responses
(6) inhibits TGF-β/Smad3 pathway on transplant rejection | (1) recurrent infections in rickets or CKD patients
(2) increased incidence of respiratory diseases, such as influenza, mycobacterium tuberculosis, and chronic respiratory diseases, such as cystic fibrosis, interstitial lung disease, and chronic obstructive pulmonary disease
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| Antiapoptosis and antfibrosis | (1) induce apoptosis via interaction between Bcl2 and Bax in breast cancer cells
(2) affect the conduction of the motor neurons and synthesis of neurotrophic factors, thus preventing damage of the neurons
(3) inhibit the growth cycle of the TGF-α/EGFR and reduce the proliferation of keratinocytes | (1) progression of cancer cells
(2) excess formation of keratin in psoriasis |
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| Cardiovascular diseases | (1) have negative feedback on renin-angiotensin system in regulating blood pressure, electrolyte and volume status
(2) have direct binding to vitamin D receptor on the myocardial cells and regulate the hypertrophy of myocardial cells
(3) have synthesis and release of atrial natriuretic peptide
(4) inhibit angiogenesis and increase matrix G1A protein synthesis, thus inhibiting inflammatory cytokines such as tumor necrosis factor and interleukin
(5) inhibit calcification of blood vessels by regulating interleukins | (1) hypertension, water retention
(2) cardiac hypertrophy, myocardial infarction, stroke, congestive heart failure, peripheral vascular disease, and atherosclerosis |
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| Kidney diseases | (1) inhibit renal interstitial myofibroblasts, inhibiting the progression to renal interstitial fibrosis | (1) renal fibrosis |
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| Diabetes mellitus (DM) | (1) prevents the destruction of pancreatic beta-cells
(2) reduces autoimmune diabetes mellitus, possibly secondary to inhibition of proinflammatory cytokines, such as tumor necrosis factor (TNF-α) | (1) earlier onset and more severe DM
(2) type I DM |
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| Immune system | (1) activates cathelicidins, an antimicrobial peptide within the lysosomes of macrophages and polymorphonuclear leukocytes | (1) increases initiation of experimental autoimmune encephalomyelitis, thyroiditis, type 1 diabetes mellitus, inflammatory bowel disease, systemic lupus erythematosus, and Lyme arthritis
(2) increases the disease activity of rheumatoid arthritis |
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| Cancers | (1) promote the transcription of cyclin-dependent kinase inhibitors, p21
(2) induce synthesis of the cyclin-dependent kinase inhibitors, p27
(3) inhibit the TGF-α/EGFR growth pathway
(4) induce the expression of C/EBPβ and prevent proliferation of LIP epidermal growth factor receptor, thus reducing EGFR-driven related cancers
(5) suppress expression of anti-apoptotic proteins such as Bcl2 of cancer cells, arrest of cell cycle in G0/G1, thus slowing proliferation of cancer cells | (1) prostate, breast, and colon cancers
(2) leukemia and other myeloproliferative disorders |
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