460 Matching Annotations
  1. Nov 2021
    1. Possible adverse effects include nausea and vomiting , diarrhea , sore mouth , decreased white blood cell count , decreased platelet count , and infusion site burning .
    2. Possible adverse effects include nausea and vomiting , diarrhea , sore mouth , decreased white blood cell count , decreased platelet count , and infusion site burning .
    3. Possible adverse effects include nausea and vomiting , diarrhea , sore mouth , decreased white blood cell count , decreased platelet count , and infusion site burning .
    4. Possible adverse effects include nausea and vomiting , diarrhea , sore mouth , decreased white blood cell count , decreased platelet count , and infusion site burning .
    5. - The active metabolite 5-fluoro-2 ' - deoxyuridine-5 ' - O-monophosphate ( F-dUMP ) , inhibits Thymidylate Synthase , resulting in the depletion of thymidine triphosphate ( TTP ) , a necessary constituent of DNA .
    6. FdUMP inhibits DNA synthesis and cell division by reducing thymidine production.Several fluorouracil metabolites incorporate into both RNA and DNA .
    7. FdUMP inhibits DNA synthesis and cell division by reducing thymidine production .
    8. Possible adverse effects include nausea and vomiting , diarrhea , sore mouth , decreased white blood cell count , decreased platelet count , and infusion site burning .
    9. Possible adverse effects include nausea and vomiting , diarrhea , sore mouth , decreased white blood cell count , decreased platelet count , and infusion site burning .
    10. The occurrence of bone marrow suppression can cause neutropenia , which may lead to infections .
    11. Some of the anti-neoplastic antibiotics also inhibit Topoisomerase 2 .
    12. Antibiotics Some of the anti-neoplastic antibiotics also inhibit Topoisomerase 2 .
    13. Doxifluridine ( 5 ' - deoxy-5-fluorouridine ) is a fluoropyrimidine derivative and oral prodrug of 5-fluorouracil , designed to circumvent the rapid degradation of 5-fluorouracil by Dihydropyrimidine Dehydrogenase in the gut wall and liver .

      DPYD inhibits Liver.

    14. Doxifluridine ( 5 ' - deoxy-5-fluorouridine ) is a fluoropyrimidine derivative and oral prodrug of 5-fluorouracil , designed to circumvent the rapid degradation of 5-fluorouracil by Dihydropyrimidine Dehydrogenase in the gut wall and liver .

      DPYD inhibits 5-fluorouracil.

    15. Carbonyl Reductase ( CBR ) catalyzes the reduction of daunorubicin to its corresponding alcohol , daunorubicinol , which changes the pharmacological properties of this cancer chemotherapeutic drug .

      CNR1 inhibits daunorubicin.

    16. Pharmacokinetics Carbonyl Reductase ( CBR ) catalyzes the reduction of daunorubicin to its corresponding alcohol , daunorubicinol , which changes the pharmacological properties of this cancer chemotherapeutic drug .

      CNR1 inhibits daunorubicin.

    17. Thymidylate Synthase inhibitors Thymidylate Synthase catalyzes the methylation of 2 ' - deoxyuridine-5 ' - monophosphate ( dUMP ) to 2 ' - deoxythymidine-5'monophosphate ( dTMP ) , which is subsequently phosphorylated to thymidine triphosphate , an essential precursor in DNA synthesis ( Fig. 2.42 ) .

      TYMS inhibits methylation.

    18. Although camptothecin and its analogs can freely enter cells via passive diffusion , their intracellular concentrations are greatly reduced by efflux pumps .
    19. Drug Resistance Although camptothecin and its analogs can freely enter cells via passive diffusion , their intracellular concentrations are greatly reduced by efflux pumps .
    20. Methyl benzyl hydrazine derivatives can suppress mitosis by prolonging interphase .

      interphase inhibits Mitosis.

    21. The therapeutic index of bis ( sulfonyl ) hydrazine compounds may therefore be more favorable.Methyl benzyl hydrazine derivatives can suppress mitosis by prolonging interphase .

      interphase inhibits Mitosis.

    22. Streptozotocin can reduce the tumor burden and ameliorate symptoms , such as hypoglycemia due to excessive Insulin secretion by insulinomata .
    23. Procarbazine inhibits MAO thus increasing the effects of sympathomimetics , tricyclic anti-depressants , and tyramine ( hypertensive crisis can be caused by the ingestion of tyramine-rich food ) .
    24. Razoxane inhibits Topoisomerase 2 without inducing DNA strand breaks , thereby inhibiting DNA synthesis and inducing cytotoxicity .

      razoxane inhibits TOP.

    25. A structural analog of p-aminobenzoic acid ( PABA ) , dapsone inhibits Dihydropteroate Synthase , resulting in a depletion of the folate pool and a reduction in the amount of thymidylate available for DNA synthesis .
    26. Allopurinol may be preferred to prevent or reverse uracil mustard induced hyperuricemia and the risk of uric acid nephropathy .
    27. Allopurinol may diminish the rate of 6-mercaptopurine degradation by competing for the oxidizing enzymes that are part of the inactivating pathway , specifically the Xanthine Oxidase mediated degradation to thiouric acid .
    28. Nitrogen mustard also damages DNA through the production of reactive nitrogen species .
    29. Mitomycin C at high concentrations also inhibits RNA and protein synthesis .
    30. This metabolite inhibits DNA Polymerase alpha , Ribonucleotide Reductase , and DNA Primase , thereby interrupting DNA synthesis and inhibiting tumor cell growth .
    31. This metabolite inhibits DNA Polymerase alpha , Ribonucleotide Reductase , and DNA Primase , thereby interrupting DNA synthesis and inhibiting tumor cell growth .
    32. These drugs inhibited adenine metabolism and later played an important role in the treatment of acute leukemia .
    33. The drug intercalates into DNA and interacts with Topoisomerase 2 , thereby inhibiting DNA reduplication and repair , as well as RNA and protein synthesis .
    34. The drug suppresses the expression of genes coding for transcription factors , heat shock proteins , and DNA repair proteins .
    35. Gemcitabine may temporarily reduce the number of white blood cells , particularly during the first 10-14 days after administration .
    36. The neurotoxicity can be reduced by intake of pyridoxine ( vitamin B6 ) , however , it adversely affects the response duration .
    37. Edatrexate inhibits Thymidylate Synthase and Glycinamide Ribonucleotide Formyl Transferase , impairing the synthesis of purine nucleotides and amino acids , and resulting in tumor cell death .

      edatrexate inhibits TYMS.

    38. Thereby exatecan inhibits DNA reduplication and triggers apoptotic cell death .
    39. As a Topoisomerase 2 inhibitor and intercalating agent , elliptinium stabilizes the cleavable complex of Topoisomerase 2 and induces DNA breakages , thereby inhibiting DNA reduplication and RNA synthesis .
    40. Cardiac toxicity may cause tachycardia or left ventricular systolic dysfunction .
    41. - Anthracyclines can directly release Cytochrome c from the mitochondria , thereby inducing apoptosis regardless of DNA damage , active signaling pathways , or P53 status .

      Anthracyclines activates TP53.

    42. - Anthracyclines can directly release Cytochrome c from the mitochondria , thereby inducing apoptosis regardless of DNA damage , active signaling pathways , or P53 status .
    43. In 1972 , when the Lasker Prize was awarded to investigators who had contributed to studies of 36 Aminopterin was synthesized by Yellapragada Subbarao at Lederle Laboratories .
    44. Severe pancytopenia can arise and sometimes lead to death .

      Pancytopenia activates Death.

    45. Patients may experience myelosuppression , including prolonged pancytopenia , which can result in aplastic anemia .
    46. It acts at an essential step along the de novo path of pyrimidine biosynthesis by inhibiting Orotidylate Decarboxylase , which suppresses the formation of uridylic acid from its carboxylated precursor , orotidylic acid .
    47. The drug administered intrapleurally , intraperitoneally , or 7 A myeloproliferative disorder that results in the over-production of red blood cells .
    48. Adverse effects include hemolysis , which may lead to hemolytic anemia , and methemoglobinemia .
    49. Adverse Effects Adverse effects include hemolysis , which may lead to hemolytic anemia , and methemoglobinemia .
    50. Adverse effects include hemolysis , which may lead to hemolytic anemia , and methemoglobinemia .
    51. Adverse Effects Adverse effects include hemolysis , which may lead to hemolytic anemia , and methemoglobinemia .
    52. Genetic testing can predict this toxicity before chemotherapy administration and can allow dose adjustment .

      Genetic Testing activates dose.

    53. Cardiotoxicity can occur due to supraventricular arrhythmia .
    54. This is likely due to poorer activation of porfiromycin by DT-Diaphorase and a greater dependence of this drug on activation by NADPH : Cytochrome P450 Reductase compared with mitomycin C ( Begleiter 2000 ) .

      NQO1 activates Porfiromycin.

    55. Low doses of adozelesin , bizelesin , or carzelesin induce cell cycle arrest , high doses induce apoptosis .
    56. thioTEPA is activated by CYP3A4 and CYP2D6 .

      CYP3A4 activates Thiotepa.

    57. Whereas both cyclophosphamide and ifosfamide are activated by Cytochromes P450 2B1 and 2C6 / 2C11 , only ifosfamide is also activated by Cytochrome P450 3A .

      CYP3A activates ifosfamide.

    58. thioTEPA is activated by CYP3A4 and CYP2D6 .

      CYP2D6 activates Thiotepa.

    59. Thymidylate Synthase catalyzes the methylation of 2 ' - deoxyuridine-5 ' - monophosphate ( dUMP ) to 2 ' - deoxythymidine-5 ' - monophosphate ( dTMP ) , which is subsequently phosphorylated to thymidine triphosphate , an essential precursor in DNA synthesis ( Fig. 2.42 ) .

      TYMS activates methylation.

    60. These DNA modifications lead to DNA fragmentation and cell death .
    61. Drug resistance may be caused by platinum efflux , detoxification through thiols , apoptosis resistance , or enhanced DNA repair .
    62. The drug is an intercalator and a Topoisomerase 2 inhibitor that prevents DNA reduplication and ultimately inhibits protein synthesis .
    63. Molecularly Targeted Therapy The cells of glioblastomata and anaplastic gliomatas secrete glutamate and also express AMPA Glutamate Receptors , which contribute to proliferation , migration and neurotoxicity .
    64. The cells of glioblastomata and anaplastic gliomatas secrete glutamate and also express AMPA Glutamate Receptors , which contribute to proliferation , migration and neurotoxicity .
    65. These events lead to apoptosis .
    66. A common adverse effect of semustine is prolonged myelosuppression , which may result in infection and bleeding .
    67. Adverse Effects A common adverse effect of semustine is prolonged myelosuppression , which may result in infection and bleeding .
    68. Ototoxicity ( tinnitus and hearing loss ) can lead to deafness .

      ototoxicity activates Deafness.

    69. The bone marrow depressant effects of uracil mustard may result in an increased incidence of microbial infections , delayed healing , and bleeding .
    70. ThioTEPA causes amenorrhea and interferes with spermatogenesis .

      Thiotepa activates amenorrhea.

    71. Thioguanine causes birth defects if taken during pregnancy .
    72. When combined with ethanol , procarbazine can cause adverse drug reactions in some patients .
    73. A common adverse effect of semustine is prolonged myelosuppression , which may result in infection and bleeding .
    74. Adverse Effects A common adverse effect of semustine is prolonged myelosuppression , which may result in infection and bleeding .
    75. As an alkylating agent , dimethylbusulfan induces neutropenia .
    76. Adverse Effects As an alkylating agent , dimethylbusulfan induces neutropenia .
    77. Polycyclic aromatic antibiotics ( anthracyclins , anthracenediones , anthrapyrazoles ) and enediynes generate free radicals through redox cycling by a mechanism that depends in part 24 The suffix - mycin is conventionally used to describe a substance derived from a bacterium in the order Actinomycetales .

      enediyne activates radical.

    78. It is caused by drug metabolites that agonize AMPA / Kainate Receptors and induce cellular acidification in cortical neurons .
    79. Iron mediated free radical reactions enable anthracyclines to produce formaldehyde ( HCHO ) from carbon cellular sources like spermine and lipids .
    80. 5-fluorouracil causes myelosuppression .
    81. Unlike other common alkylating agents , cyclophosphamide can occasionally induce remission in acute childhood leukemias , and it can be used to prolong remission .
    82. 3,6 - diaziridinyl-1 ,4 - benzoquinone ( DZQ ) causes the increased expression of P21CIP1 / WAF1 , an inhibitor of Cyclin-Dependent Kinases .

      benzoquinone activates CDKN1A.

    83. The pathway synthesizes inosine monophosphate from ribose-5-phosphate , the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine .

      picloram activates IMP.

    84. Carboplatin causes thrombocytopenia with a nadir of 10-14 days .
    85. Carboplatin also leads to alopecia , fatigue , and abnormal blood electrolyte levels ( magnesium , sodium , potassium , calcium ) .

      carboplatin activates Fatigue.

    86. Carboplatin also leads to alopecia , fatigue , and abnormal blood electrolyte levels ( magnesium , sodium , potassium , calcium ) .

      carboplatin activates Alopecia.

    87. In chronic granulocytic leukemia , busulfan can induce remission in 90 % of patients after the initial course of therapy .

      busulfan activates remission.

    88. - Actinomycin D causes single strand DNA breaks , possibly via a free radical intermediate or an interaction with Topoisomerase 2 .
    89. Carbonyl Reductase ( CBR ) catalyzes the reduction of daunorubicin to its corresponding alcohol , daunorubicinol , which changes the pharmacological properties of this cancer chemotherapeutic drug .
    90. 3,6 - diaziridinyl-1 ,4 - benzoquinone ( DZQ ) causes the increased expression of P21CIP1 / WAF1 , an inhibitor of Cyclin-Dependent Kinases .
    91. FdUMP inhibits DNA synthesis and cell division by reducing thymidine production .
    92. Thereby exatecan inhibits DNA reduplication and triggers apoptotic cell death .
    93. Fotemustine may cause retinal atrophy or retinal detachment .
  2. Sep 2021
    1. In contrast , in adult mice TLR2 / TLR4 activation on pericryptal macrophages by exogenous HA or other TLR2 / TLR4 agonists results in CXCL12 production resulting in the migration of COX-2 expressing MSCs .

      TLR2 activates TLR4.

    2. TLR4 activation by LPS requires a TLR4-MD2 complex , LPS binding protein , and CD14 which delivers LPS to the TLR4-MD2 complex ( 33 , 34 ) .
    3. TLR4 activation by LPS and LMW-HA require different accessory molecules .
    4. Although both LMW-HA and LPS bind to TLR4 , the results of TLR4 activation by LMW-HA and LPS are not identical .
    5. Activation of TLR2 by LTA or activation of TLR4 by LPS or HA results in the release of the chemokine CXCL12 , which binds to CXCR4 on COX-2 expressing MSCs .
    6. Although there are differences in the accessory molecules involved in TLR4 activation by LPS and LMW - HA , TLR4 activation by either one promotes wound healing ( 12 , 27 , 28 , 33 ) .
    7. TLR4 activation by HA also plays a role in wound repair ( 22 ) .

      hyaluronic acid activates TLR4.

    8. TLR4 activation by HA also affects the immune response in ischemia - reperfusion injury in the kidney and in acute allograft rejection in a skin transplant model ( 8) .

      hyaluronic acid activates TLR4.

    9. Moreover , in contrast to wound repair where activation of TLRs by both microbial PAMPs and non-microbial agents , such as HA , play a role ( 11 , 12 ) , intestinal growth is driven only by TLR4 activation by the nonmicrobial agent , HA ( 17 ) .

      hyaluronic acid activates TLR4.

    1. PIK3CA promoted bladder cancer progression by activating EMT related makers - - Snail , beta-catenin , vimentin and E-cadherin .
    2. PIK3CA Promote Bladder Cancer Progression by Activating EMT Related Makers - - Snail , E-cadherin , Vimentin , and beta-Catenin Although the functional role of PIK3CA in EMT has been investigated in several cancers ( 39 ) , there are only a few reports in bladder cancer demonstrating involvement of PIK3CA in the process of EMT .
    3. In our study , we found activation of PIK3CA resulted in an increase in the expression of Snail and a decrease in the expression of E-cadherin at the mRNA and protein level , while inhibition of PIK3CA had the opposite effect .

      PIK3CA activates SNAI1.

    4. For example , the conclusion that CUX1 stimulates the expression of PIK3CA requires more experiments to further demonstrate .

      CUX1 activates PIK3CA.

    5. Together , the above results demonstrated that CUX1 stimulated transcription activity via direct interaction with the binding site of PIK3CA promoter .
    1. In line with these findings , gene ontology analysis of AR-ERG co-bound gene signature in VCaP cells indicated that the most striking transcriptional changes were linked to cellular differentiation and cell cycle arrest that are directly induced by DHT and repressed by ERG ( e.g ., HOXA genes , CDKN1A / p21 , Fig. 1d , Fig. 3b , and Supplementary Fig. 5d ) .

      ERG inhibits cell cycle.

    2. ZMYND11 induces AR signaling pathway and represses ERG activity Next , we assessed if ZMYND11 protein upregulation also contributed to the synthetic sick relationship .

      ZMYND11 inhibits ERG.

    3. ZMYND11 induces AR signaling pathway and represses ERG activity .

      ZMYND11 inhibits ERG.

    1. RPL11 and RPL5 suppress P53 degradation via binding to MDM2 .

      RPL5 inhibits TP53.

    2. The results showed that the half-life of P53 in cells transfected with RPL11 or RPL5 overexpression vector was prolonged compared with control vector-transfected cells , indicating that RPL11 and RPL5 could inhibit P53 degradation ( Fig. 4e ) .

      RPL5 inhibits TP53.

    3. RPL11 and RPL5 suppress P53 degradation via binding to MDM2 .

      RPL11 inhibits TP53.

    4. The results showed that the half-life of P53 in cells transfected with RPL11 or RPL5 overexpression vector was prolonged compared with control vector-transfected cells , indicating that RPL11 and RPL5 could inhibit P53 degradation ( Fig. 4e ) .

      RPL11 inhibits TP53.

    5. These findings suggested that RPL11 and RPL5 could inhibit breast cancer cell proliferation and induce apoptosis .
    6. RPL11 and RPL5 inhibits breast cancer cell proliferation and induced apoptosis .
    1. Moreover , Rb1 activated the PI3K / AKT pathway , down-regulated Cleaved caspase-3 and Bax , and up-regulated Bcl-2 expression .

      RB1 activates BCL2.

    2. Moreover , Rb1 activated the PI3K / AKT pathway , down-regulated Cleaved caspase-3 and Bax , and up-regulated Bcl-2 expression .

      RB1 activates BCL2.

    3. Moreover , Rb1 activated the PI3K / AKT pathway , down-regulated Cleaved caspase-3 and Bax , and up-regulated Bcl-2 expression .

      RB1 activates PI3K.

    4. Moreover , Rb1 activated the PI3K / AKT pathway , down-regulated Cleaved caspase-3 and Bax , and up-regulated Bcl-2 expression .

      RB1 activates PI3K.

    1. Heme oxygenase ( HO ) is a stress-inducing enzyme that catalyzes heme to produce free iron , carbon monoxide ( CO ) , and biliverdin [ 7 ] .

      heme activates carbon monoxide.

    2. Heme oxygenase ( HO ) is a stress-inducing enzyme that catalyzes heme to produce free iron , carbon monoxide ( CO ) , and biliverdin [ 7 ] .

      heme activates biliverdin.

    1. Newer studies add to this small body of data , including an intriguing study where a novel PTEN / ARID4B / PI3K pathway in which PTEN inhibits the expression of ARID4B was characterised .

      PTEN inhibits ARID4B.

    2. PTEN inhibits ARID4B expression and thus prevents the transcriptional activation of ARID4B transcriptional targets PIK3CA and PIK3R2 ( PI3K subunits ) 79 .

      PTEN inhibits ARID4B.

    1. CKIotadelta promotes the interaction and degradation of LATS1 by SPOP It has been previously reported that proper substrate phosphorylation is necessary before substrate ubiquitination and degradation by SCF type of E3 ligases including FBW7 and beta-TRCP .

      SPOP activates LATS1.

  3. Aug 2021
    1. Dong et al. found that NLRP3 inhibits senescence and enables replicative immortality through regulating the Wnt / beta-catenin pathway via the thioredoxin-interacting protein ( TXNIP ) / NLRP3 axis ( 74 ) .
    2. The knockdown of NLRP3 significantly reduces the proliferation , clonogenicity , invasion and migration in both Ishikawa and HEC-1A cells , while in contrast , NLRP3 overexpression enhances the proliferation , migration and invasion in both Ishikawa and HEC-1A cells and furthermore , increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells .
    3. Inhibition of NLRP3 suppresses the proliferation , migration and invasion , and promotes apoptosis in glioma cells , while in contrast , increased expression of NLRP3 significantly enhances the proliferation , migration and invasion as well as attenuating apoptosis in glioma cells ( 56 ) ( Table 2 ) .
    4. The role of NLRP3 in promoting invasion has been demonstrated with human endometrial cancer cell lines such as Ishikawa and HEC-1A cells , where knockdown of NLRP3 significantly reduces proliferation , clonogenicity , invasion and migration .
    5. Collectively , these results indicate that upregulated NLRP3 expression promotes the progression of endometrial cancer ( 55 ) .

      NLRP3 activates Dientamoebiasis.

    6. Liu et al. concluded that the upregulation of NLRP3 expression promotes the progression of endometrial cancer ; therefore , NLPR3 inflammasome might be a new therapeutic target for endometrial cancer ( 55 ) .

      NLRP3 activates Dientamoebiasis.

    7. NLRP3 enhances IL-1beta , subsequently activating NF-kappaB , and initiates JNK signaling to cause proliferation and invasion in gastric cancer ( 21 ) .

      NLRP3 activates IL1B.

    8. Consistently , knockdown of NLRP3 induces cell apoptosis in MCF-7 cells and decreases cell migration ( 54 ) ; nevertheless , in other cell-types , NLRP3 inflammasome may pharmacologically repress proliferation and metastasis of hepatic cell carcinoma ( HCC ) ( 21 ) ( Table 4 ) .

      NLRP3 activates cell migration.

    9. NLRP3 enhances IL-1beta , subsequently activating NF-kappaB , and initiates JNK signaling to cause proliferation and invasion in gastric cancer ( 21 ) .

      NLRP3 activates NFkappaB.

    10. Moreover , NLRP3 downstream , IL-1beta , also stimulates the production of ROS that , in turn , induces DNA damage and cancer development in CRC ( 42 ) ( Table 2 ) .
    1. KLK8 degrades VE-cadherin , thereby promoting plakoglobin nuclear translocation The KLK family is considered to cleave kininogens to release kinin 15 .

      KLK8 inhibits CDH5.

    2. As shown in Figure 11A , it was found that high glucose led to a significant increase in the association of plakoglobin with p53 , which was blocked by KLK8 knockdown .

      KLK8 activates TP53.

    3. We then generated a KLK8 report gene by cloning the promoter of human KLK8 into the pGL3 vector , thereby further confirming that high glucose stimulates KLK8 expression through the Sp-1 site in the KLK8 gene .

      glucose activates KLK8.

    4. It was found that the mRNA and protein expression levels of KLK8 were significantly upregulated in a dose-dependent manner in high glucose-treated HCAECs compared with those of normal glucose-treated HCAECs ( Figure 8A-B ) , suggesting that high glucose stimulated KLK8 expression at the transcriptional level .

      glucose activates KLK8.

    1. Downregulation of PTEN expression or inhibiting its biologic activity improves heart function , promotes cardiomyocytes proliferation , reduces cardiac fibrosis as well as dilation , and inhibits apoptosis following ischemic stress such as myocardial infarction .

      PTEN activates apoptotic process.

  4. Jul 2021
    1. The C2 domain ( amino acids 186-351 ) can bind phospholipid membrane independent of calcium because it lacks the canonical Ca2 + chelating residues in vitro , which makes PTEN inhibit cell migration [ 31 ] .

      PTEN inhibits cell migration.

    2. Recently , it has been found that the impairment of PARK2 can induce the suppression of PTEN by S-nitrosylation through increase the level of NO [ 55 ] .

      PRKN activates PTEN.

    3. The C2 domain ( amino acids 186-351 ) can bind phospholipid membrane independent of calcium because it lacks the canonical Ca2 + chelating residues in vitro , which makes PTEN inhibit cell migration [ 31 ] .

      PTEN inhibits cell migration.

    4. Recently , it has been found that the impairment of PARK2 can induce the suppression of PTEN by S-nitrosylation through increase the level of NO [ 55 ] .

      PRKN activates PTEN.

    1. Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage : Involvement of AKT / FoxO3a / ATG-Mediated Autophagy .
    2. Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage : Involvement of AKT / FoxO3a / ATG-Mediated Autophagy Spontaneous intracerebral hemorrhage ( ICH ) commonly causes secondary hippocampal damage and delayed cognitive impairments , but the mechanisms remain elusive .
    3. However , blockage of PTEN prominently abolished these ATG transcriptions and subsequent autophagy induction .
    4. Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage : Involvement of AKT / FoxO3a / ATG-Mediated Autophagy .
    5. Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage : Involvement of AKT / FoxO3a / ATG-Mediated Autophagy Spontaneous intracerebral hemorrhage ( ICH ) commonly causes secondary hippocampal damage and delayed cognitive impairments , but the mechanisms remain elusive .
    6. However , blockage of PTEN prominently abolished these ATG transcriptions and subsequent autophagy induction .
    1. Our study showed that hypoxia increased the production of S100A8 in microglia .

      Hypoxia activates S100A8.

    2. FACS analysis showed that the increase of S100A8 levels in microglia by hypoxia promoted neuronal apoptosis , which was confirmed by immunofluorescence .

      Hypoxia activates S100A8.

    3. In our study , the increase of IL-1beta expression by S100A8 indicated that S100A8 was involved in the priming signal for NLRP3 inflammasome assembly in microglia ( Figure 2B ) .

      S100A8 activates IL1B.

    4. Our study showed that hypoxia increased the production of S100A8 in microglia .

      Hypoxia activates S100A8.

    5. FACS analysis showed that the increase of S100A8 levels in microglia by hypoxia promoted neuronal apoptosis , which was confirmed by immunofluorescence .

      Hypoxia activates S100A8.

    1. Newer studies add to this small body of data , including an intriguing study where a novel PTEN / ARID4B / PI3K pathway in which PTEN inhibits the expression of ARID4B was characterised .

      PTEN inhibits ARID4B.

    2. PTEN inhibits ARID4B expression and thus prevents the transcriptional activation of ARID4B transcriptional targets PIK3CA and PIK3R2 ( PI3K subunits ) 79 .

      PTEN inhibits ARID4B.

    1. Increased mitochondrial Ca2 + concentration ( [ Ca2 + ] ) , in addition to augmented ROS production , induces a reduction of the mitochondrial membrane potential ( DeltaPsim ) in melanocytes and the circulating mononuclear cells of vitiligo patients ( 44 , 72 ) .

      CA2 inhibits Melanocytes.

    2. These events can thus result in the alteration of the Treg / cytotoxic T cell ratio , impaired Treg differentiation , and increased inflammation in vitiligo .
    3. Increased mitochondrial Ca2 + concentration ( [ Ca2 + ] ) , in addition to augmented ROS production , induces a reduction of the mitochondrial membrane potential ( DeltaPsim ) in melanocytes and the circulating mononuclear cells of vitiligo patients ( 44 , 72 ) .
    4. High concentrations of H2O2 disrupt melanin synthesis by inhibiting tyrosinase and dihydropteridine reductase ( 71 ) .
    5. IFN-gamma is also responsible for stimulating the production of CXCL9 and CXCL10 in keratinocytes , which engages the chemokine receptor CXCR3 on melanocytes and triggers apoptosis , further contributing to the disease ( 127 ) .
    6. In vitiligo , stressed melanocytes increase the expression of Hsp70 , which binds and transports potentially immunogenic antigens to the MHC complex , allowing for their presentation on the cell surface to cytotoxic T cells ( 109 ) .

      Melanocytes activates HSPA.

    7. Interestingly , keratinocytes in vitiligo lesions aberrantly produce IL-1 , IL-6 , and TNF-alpha , which inhibit melanocyte function ( 65 , 66 ) and elicit an inflammatory response .
    8. Blockade of IL-15Rbeta ( CD122 ) reduces IFN-gamma production and can eliminate skin TRM and reverse vitiligo ( 133 ) .

      IL2RB activates IFNG.

    9. In this case , NKG2D enhances TCR activation and thus , T cell function ( 18-20 ) .

      KLRK1 activates TCR.

    10. ROS production is also increased by TNF-alpha , further promoting stress signals in vitiligo melanocytes .
    11. These events , in combination with reduced suppression by dysfunctional Treg cells , result in the onset , perpetuation , and spreading of vitiligo .

      event activates Vitiligo.

    12. Exposure to UV light and its absorption by melanocytes causes photo-oxidation of melanin , generating superoxide radicals ( 54 ) , which in turn induce melanin biosynthesis ( 56 ) .
    13. Calreticulin , an endoplasmic reticulum ( ER ) protein that regulates Ca2 + homeostasis and signaling , is also modulated by H2O2 , which increases calreticulin expression and translocation to the cell surface of melanocytes .

      hydrogen peroxide activates CALR.

    14. Calreticulin , an endoplasmic reticulum ( ER ) protein that regulates Ca2 + homeostasis and signaling , is also modulated by H2O2 , which increases calreticulin expression and translocation to the cell surface of melanocytes .
    1. In addition , resveratrol as well as oleuropein aglycone and hydroxytyrosol significantly reduce the activation of NFkappaB in LPS-stimulated human umbilical vein endothelial cells ( HUVECs ) as determined by electrophoretic mobility shift assay [ 87 ] .
    2. In addition , resveratrol as well as oleuropein aglycone and hydroxytyrosol significantly reduce the activation of NFkappaB in LPS-stimulated human umbilical vein endothelial cells ( HUVECs ) as determined by electrophoretic mobility shift assay [ 87 ] .
    3. Similarly , other polyphenols , such as luteolin , chrysin , hesperidin , naringin and kaempferol have been shown to reduce inflammation by interfering with MAPKs pathways [ 107-109 ] .
    4. In addition , resveratrol as well as oleuropein aglycone and hydroxytyrosol significantly reduce the activation of NFkappaB in LPS-stimulated human umbilical vein endothelial cells ( HUVECs ) as determined by electrophoretic mobility shift assay [ 87 ] .
    5. Polyphenols in the treatment of autoimmune diseases In addition to protecting body from infections and diseases , the immune system produces auto-antibodies that can cause complex autoimmune disorders , such as Type I diabetes , primary biliary cirrhosis , rheumatoid arthritis , and multiple sclerosis , to name a few .
    6. However , under certain circumstances , the immune system may produce auto-antibodies against its own cells , leading to autoimmune diseases .
    7. Curcumin has also been reported to reactivate the neprilysin gene ( a strong inhibitor of Akt ) through CpG demethylation , leading to Akt inhibition and the subsequent inhibition of NFkappaB in mouse neuroblastoma N2a cells [ 132 ] .

      curcumin activates MME.

    8. Also , resveratrol induced neuroprotection in rats undergoing ischemia / reperfusion induced cerebral damage by activating the PI3K / Akt survival pathway [ 119 ] .
    9. Among the various polyphenols , resveratrol has been shown to be a strong activator of SIRT1 , resulting in the inhibition of NFkappaB and its downstream genes , such as COX-2 and iNOS [ 123 , 124 ] .

      resveratrol activates SIRT1.

    10. Once in the cytoplasm , AA is targeted by various enzymes such as COX and LOX to generate prostaglandins ( PGs ) and thromboxanes A2 or hydroxyeicosatetraenoic acids ( HETEs ) and leukotrienes ( LTs ) , respectively [ 69 ] .
    1. The retention of tissue-resident memory T cells is mediated by TGF-beta , which up-regulates CD103 expression and down-regulates CCR7 expression .

      TGFB inhibits CCR7.

    2. High-fat diet upregulated E-FABP expression and promote skin inflammation , suggesting the role of lipid metabolism in immune regulation ( 105 ) .
    3. High-fat diet upregulated E-FABP expression and promote skin inflammation , suggesting the role of lipid metabolism in immune regulation ( 105 ) .

      Diet, High-Fat activates FABP5.

    4. Endothelial cells increase the expression of adhesion molecules ; CD54 ( ICAM-1 ) and CD106 ( VCAM-1 ) , which guide T cell entry into the tissue .
    5. These mediators stimulate keratinocytes to produce TNF-alpha , IL-8 , and vascular endothelial growth factor , thereby promoting inflammation , neutrophil recruitment , and angiogenesis ( 129 ) .

      Keratinocytes activates CXCL8.

    6. These mediators stimulate keratinocytes to produce TNF-alpha , IL-8 , and vascular endothelial growth factor , thereby promoting inflammation , neutrophil recruitment , and angiogenesis ( 129 ) .
    7. These mediators stimulate keratinocytes to produce TNF-alpha , IL-8 , and vascular endothelial growth factor , thereby promoting inflammation , neutrophil recruitment , and angiogenesis ( 129 ) .

      Keratinocytes activates VEGF.

    8. Thus , CD8 + CD103 + TRM cells efficiently produce IL-17A .

      ITGAE activates IL17A.

    9. In contrast , in the xenotransplantation model of psoriasis , blocking CD49a inhibits T cell migration into the epidermis , resulting in a decrease of TRM cells and prevention of psoriasis development ( 76 ) .

      ITGA1 activates T cell migration.

    10. Th17-derived cytokines , IL-17A , IL-17F and IL-22 , induce epidermal acanthosis , which represents an intriguing histological finding of psoriasis and results from the proliferation of epidermal keratinocytes .
    11. Th17-derived cytokines , IL-17A , IL-17F and IL-22 , induce epidermal acanthosis , which represents an intriguing histological finding of psoriasis and results from the proliferation of epidermal keratinocytes .
    12. Th17-derived cytokines , IL-17A , IL-17F and IL-22 , induce epidermal acanthosis , which represents an intriguing histological finding of psoriasis and results from the proliferation of epidermal keratinocytes .
    13. They sense autoantigen in the skin long after stabilization of disease and produce IFN-gamma , which further induces CXCL9 , and CXCL10 production .

      IP-10 production activates CXCL9.

    14. TGF-beta induces CD103 expression on activated CD8 + T cells , but not CD4 + T cells , and leads to CD103-mediated adhesion of CD8 + T cells , but not CD4 + T cells , to monolayer human keratinocyte cultures ( 68 ) .

      TGFB activates ITGAE.

    15. The retention of tissue-resident memory T cells is mediated by TGF-beta , which up-regulates CD103 expression and down-regulates CCR7 expression .

      TGFB activates ITGAE.

    16. Since IL-12 can induce IFN-gamma production and CD49a expression , it is tempting to speculate that in the psoriasis context , IL-17A-producing TRM cells , which preferentially express IL-23R ( 74 ) , downregulate their CD49a due to a greater influence of IL-23 over IL-12 .

      IL12 activates ITGA1.

    17. Since IL-12 can induce IFN-gamma production and CD49a expression , it is tempting to speculate that in the psoriasis context , IL-17A-producing TRM cells , which preferentially express IL-23R ( 74 ) , downregulate their CD49a due to a greater influence of IL-23 over IL-12 .

      IL12 activates IFNG.

    18. Thus , CD8 + CD103 + TRM cells efficiently produce IL-17A .

      CD8 activates IL17A.

    19. The ligand for CCR8 , CCL1 , is preferentially expressed in human skin , and keratinocyte-derived prostaglandin E2 and vitamin D3 can induce CCR8 expression by CD8 + T cells , suggesting that it may involve in TRM localization in skin ( 62 , 63 ) .

      calciol activates CCR8.