Xenoestrogens in aquatic ecosystems

Pravilan rad endokrinog sustava neophodan je za sklad i ravnotežu unutar svakog organizma. Danas, kao posljedica zagađenja, u vodenim ekosustavima postoji velik broj tvari koje imaju sposobnost uplitanja u pravilno funkcioniranje endokrinog sustava. Mnogo je potencijalnih izvora endokrinih modulatora, od raznih industrijskih postrojenja, preko poljoprivrede pa sve do nas samih. Smatra se da su među najvažnijima ksenoestrogeni, tvari sposobne za vezanje na estrogenski receptor zbog njegove slabe specifičnosti. Ksenoestrogeni uzrokuju niz deformacija organa reproduktivnog sustava, a time i smanjenje uspješnosti oplodnje i preživljavanje potomaka u mnogih životinjskih vrsta čije je stanište kontaminirano. I sam čovjek izložen je tim tvarima, direktno, koristeći kontaminiranu vodu, ili indirektno kao dio hranidbenog lanca.Proper function of endocrine system is essential for inner harmony and balance of every organism. As an outcome of environmental pollution, there is a huge amount of substances in aquatic ecosystems, which are capable of interfering in function of endocrine system. There are many potential sources of endocrine modulators, industry, agriculture and even ourselves. The most significant endocrine modulators are considered to be xenoestrogens, substances capable of binding to estrogen receptor because of its low specificity. Xenoestrogens cause number of reproductive organ deformations which lead to decrease in fertility success and offspring viability of many animal species inhabitating contaminated theritory. Even human population is exposed to those substances, either directly by using contaminated water or indirectly as a member of a food chain

Xenoestrogens in aquatic ecosystems

Pravilan rad endokrinog sustava neophodan je za sklad i ravnotežu unutar svakog organizma. Danas, kao posljedica zagađenja, u vodenim ekosustavima postoji velik broj tvari koje imaju sposobnost uplitanja u pravilno funkcioniranje endokrinog sustava. Mnogo je potencijalnih izvora endokrinih modulatora, od raznih industrijskih postrojenja, preko poljoprivrede pa sve do nas samih. Smatra se da su među najvažnijima ksenoestrogeni, tvari sposobne za vezanje na estrogenski receptor zbog njegove slabe specifičnosti. Ksenoestrogeni uzrokuju niz deformacija organa reproduktivnog sustava, a time i smanjenje uspješnosti oplodnje i preživljavanje potomaka u mnogih životinjskih vrsta čije je stanište kontaminirano. I sam čovjek izložen je tim tvarima, direktno, koristeći kontaminiranu vodu, ili indirektno kao dio hranidbenog lanca.Proper function of endocrine system is essential for inner harmony and balance of every organism. As an outcome of environmental pollution, there is a huge amount of substances in aquatic ecosystems, which are capable of interfering in function of endocrine system. There are many potential sources of endocrine modulators, industry, agriculture and even ourselves. The most significant endocrine modulators are considered to be xenoestrogens, substances capable of binding to estrogen receptor because of its low specificity. Xenoestrogens cause number of reproductive organ deformations which lead to decrease in fertility success and offspring viability of many animal species inhabitating contaminated theritory. Even human population is exposed to those substances, either directly by using contaminated water or indirectly as a member of a food chain

Xenoestrogens in aquatic ecosystems

Pravilan rad endokrinog sustava neophodan je za sklad i ravnotežu unutar svakog organizma. Danas, kao posljedica zagađenja, u vodenim ekosustavima postoji velik broj tvari koje imaju sposobnost uplitanja u pravilno funkcioniranje endokrinog sustava. Mnogo je potencijalnih izvora endokrinih modulatora, od raznih industrijskih postrojenja, preko poljoprivrede pa sve do nas samih. Smatra se da su među najvažnijima ksenoestrogeni, tvari sposobne za vezanje na estrogenski receptor zbog njegove slabe specifičnosti. Ksenoestrogeni uzrokuju niz deformacija organa reproduktivnog sustava, a time i smanjenje uspješnosti oplodnje i preživljavanje potomaka u mnogih životinjskih vrsta čije je stanište kontaminirano. I sam čovjek izložen je tim tvarima, direktno, koristeći kontaminiranu vodu, ili indirektno kao dio hranidbenog lanca.Proper function of endocrine system is essential for inner harmony and balance of every organism. As an outcome of environmental pollution, there is a huge amount of substances in aquatic ecosystems, which are capable of interfering in function of endocrine system. There are many potential sources of endocrine modulators, industry, agriculture and even ourselves. The most significant endocrine modulators are considered to be xenoestrogens, substances capable of binding to estrogen receptor because of its low specificity. Xenoestrogens cause number of reproductive organ deformations which lead to decrease in fertility success and offspring viability of many animal species inhabitating contaminated theritory. Even human population is exposed to those substances, either directly by using contaminated water or indirectly as a member of a food chain

Murine CMV Expressing the High Affinity NKG2D Ligand MULT-1: A Model for the Development of Cytomegalovirus-Based Vaccines

The development of a vaccine against human cytomegalovirus (CMV) has been a subject of long-term medical interest. The research during recent years identified CMV as an attractive vaccine vector against infectious diseases and tumors. The immune response to CMV persists over a lifetime and its unique feature is the inflationary T cell response to certain viral epitopes. CMV encodes numerous genes involved in immunoevasion, which are non-essential for virus growth in vitro. The deletion of those genes results in virus attenuation in vivo, which enables us to dramatically manipulate its virulence and the immune response. We have previously shown that the murine CMV (MCMV) expressing RAE-1γ, one of the cellular ligands for the NKG2D receptor, is highly attenuated in vivo but retains the ability to induce a strong CD8+ T cell response. Here, we demonstrate that recombinant MCMV expressing high affinity NKG2D ligand murine UL16 binding protein-like transcript (MULT-1) (MULT-1MCMV) inserted in the place of its viral inhibitor is dramatically attenuated in vivo in a NK cell-dependent manner, both in immunocompetent adult mice and in immunologically immature newborns. MULT-1MCMV was more attenuated than the recombinant virus expressing RAE-1γ. Despite the drastic sensitivity to innate immune control, MULT-1MCMV induced an efficient CD8+ T cell response to viral and vectored antigens. By using in vitro assay, we showed that similar to RAE-1γMCMV, MULT-1 expressing virus provided strong priming of CD8+ T cells. Moreover, MULT-1MCMV was able to induce anti-viral antibodies, which after passing the transplacental barrier protect offspring of immunized mothers from challenge infection. Altogether, this study further supports the concept that CMV expressing NKG2D ligand possesses excellent characteristics to serve as a vaccine or vaccine vector

ROLE OF NKG2D LIGANDS OF DIFFERENT AFFINITIES IN THE RECOMBINANT MOUSE CYTOMEGALOVIRUS INFECTION AND VACCINE DEVELOPMENT

Cilj istraživanja: NKG2D je aktivacijski receptor na stanicama NK i kostimulacijski receptor na limfocitima T. Stanični ligandi za receptor NKG2D su razvojno i tkivno diferencijalno izražene molekule s različitim afinitetom za isti receptor. Humani citomegalovirus (HCMV) je široko rasprostranjen herpesvirus koji potiče stvaranje svojstvenog odgovora limfocita T karakteriziranog akumulacijom virus-specifičnih stanica efektorskih obilježja što ga čini dobrim kandidatom za razvoj cjepiva. Jedno od nužnih karakteristika svakog živog cjepiva je da bude sigurno za primjenu pa smo u našim prethodnim istraživanjima razvili novi koncept cjepiva na modelu mišjeg CMV-a (MCMV) koji izražava ligand za receptor NKG2D, RAE-1γ (RAE-1γMCMV) umjesto njegovog virusnog inhibitora. Kako je MULT1 mišji NKG2D ligand najjačeg afiniteta za receptor, konstruirali smo rekombinantni MCMV u kojemu je gen za MULT1 umetnut na mjestu njegovog virusnog inhibitora (MULT1MCMV) i komparativnim pristupom smo ispitali imunosni odgovor i imunosnu kontrolu RAE-1γMCMV-a i MULT1MCMV-a in vivo te odredili njihovu sposobnost poticanja zaštitne imunosti. Materijal i metode: Kako bi ispitali kontrolu i imunosni odgovor na MULT1MCMV in vivo, inficirali smo odrasle i novookoćene miševe s MCMV-om, RAE-1γMCMV-om i MULT1MCMV-om te pratili virusni titar u organima inficiranih životinja i fenotipski okarakterizirali stanice NK i CD8 limfocite T. Zaštitnu imunost CD8 limfocita T smo ispitali adoptivnim prijenosom stanica iz imunih životinja u naivne imunokompromitirane primatelje koje smo potom inficirali MCMV-om i pratili virusni titar u organima. Testom antigenske prezentacije in vitro i eksperimentima na kimerama koštane srži miševa divljeg tipa i NKG2D-/- ispitali smo ulogu kostimulacije CD8 limfocita T putem receptora NKG2D nakon infekcije s virusima koji izražavaju NKG2D ligande. Rezultati: MULT1MCMV bio je atenuiran in vivo od strane stanica NK u odraslim i novookoćenim miševima, čak i jače od RAE-1γMCMV-a u određenim eksperimentalnim uvjetima. Unatoč atenuaciji, MUTL1MCMV je zadržao imunogeničnost i inducirao je antigen-specifičan odgovor CD8 limfocita T i protuvirusnu humoralnu imunost sličnih obilježja kao i infekcija MCMV-om i RAE-1γMCMV-om. Potvrdili smo da kostimulacijski signal putem receptora NKG2D pojačava odgovor CD8 limfocita T nakon infekcije s virusima koji izražavaju NKG2D ligande. Zaključak: MULT1MCMV je atenuiran in vivo čak i jače od MCMV-a koji izražava NKG2D ligand slabijeg afiniteta. Također, zadržao je imunogeničnost i potiče zaštitnu stečenu imunost i kao takav pokazuje povoljna obilježja cjepiva.Objectives: NKG2D is an activating receptor on NK cells and costimulatory receptor on T cells. Cellular ligands for this receptor are differentially expressed during the development and in the tissues and have different affinity for the receptor. Human cytomegalovirus (HCMV) is a widely spread herpesvirus which induces unique T cell response characterized by accumulation of virus-specific T cells with effector properties. This feature makes this virus a good vaccine candidate. One of the critical characteristics of every live vaccine is safety, so in our previous research we developed a new approach in designing vaccine based on mouse CMV (MCMV) expressing NKG2D ligand RAE-1γ instead of its viral inhibitor. Since MULT1 is an NKG2D ligand of highest affinity for the receptor, we constructed MCMV expressing this ligand instead of its viral inhibitor (MULT1MCMV) and compared it with RAE-1γMCMV in terms of viral control, immunobiology in vivo and explored their protective capacity as a vaccine. Material and Methods: To examine viral control and immune response to MULT1MCMV in vivo, we infected adult and newborn mice with MCMV, RAE-1γMCMV and MULT1MCMV and followed viral titer in organs of infected animals and did phenotypic analysis of NK cells and CD8 T cells. We tested protective immunity by adoptive transfer of CD8 T cells from immunized mice into naïve recipients which were subsequently infected with MCMV and analyzed viral titer in their organs. By using in vitro antigen presentation assay and bone marrow chimeras of wild type and NKG2D-/- mice we examined the role of NKG2D costimulation on CD8 T cells after infection with recombinant viruses expressing NKG2D ligands. Results: MULT1MCMV was attenuated in vivo by NK cells in NKG2D-dependent manner in both adult and newborn mice, even more strongly than RAE1-γMCMV in certain experimental conditions. Despite attenuation, MULT1MCMV was immunogenic and induced antigen-specific CD8 T cell response and anti-viral humoral response, comparable to infection with MCMV and RAE-1γMCMV. We showed that costimulatory signal via NKG2D receptor on CD8 T cells is able to boost their response after infection with recombinant viruses expressing NKG2D ligands. Conclusion: MULT1MCMV is attenuated in vivo even stronger than MCMV expressing NKG2D ligand of lower affinity, RAE-1γ. Moreover, it retained its immunogenicity and was able to induce protective adaptive immunity and as such shows excellent vaccine properties

ROLE OF NKG2D LIGANDS OF DIFFERENT AFFINITIES IN THE RECOMBINANT MOUSE CYTOMEGALOVIRUS INFECTION AND VACCINE DEVELOPMENT

Cilj istraživanja: NKG2D je aktivacijski receptor na stanicama NK i kostimulacijski receptor na limfocitima T. Stanični ligandi za receptor NKG2D su razvojno i tkivno diferencijalno izražene molekule s različitim afinitetom za isti receptor. Humani citomegalovirus (HCMV) je široko rasprostranjen herpesvirus koji potiče stvaranje svojstvenog odgovora limfocita T karakteriziranog akumulacijom virus-specifičnih stanica efektorskih obilježja što ga čini dobrim kandidatom za razvoj cjepiva. Jedno od nužnih karakteristika svakog živog cjepiva je da bude sigurno za primjenu pa smo u našim prethodnim istraživanjima razvili novi koncept cjepiva na modelu mišjeg CMV-a (MCMV) koji izražava ligand za receptor NKG2D, RAE-1γ (RAE-1γMCMV) umjesto njegovog virusnog inhibitora. Kako je MULT1 mišji NKG2D ligand najjačeg afiniteta za receptor, konstruirali smo rekombinantni MCMV u kojemu je gen za MULT1 umetnut na mjestu njegovog virusnog inhibitora (MULT1MCMV) i komparativnim pristupom smo ispitali imunosni odgovor i imunosnu kontrolu RAE-1γMCMV-a i MULT1MCMV-a in vivo te odredili njihovu sposobnost poticanja zaštitne imunosti. Materijal i metode: Kako bi ispitali kontrolu i imunosni odgovor na MULT1MCMV in vivo, inficirali smo odrasle i novookoćene miševe s MCMV-om, RAE-1γMCMV-om i MULT1MCMV-om te pratili virusni titar u organima inficiranih životinja i fenotipski okarakterizirali stanice NK i CD8 limfocite T. Zaštitnu imunost CD8 limfocita T smo ispitali adoptivnim prijenosom stanica iz imunih životinja u naivne imunokompromitirane primatelje koje smo potom inficirali MCMV-om i pratili virusni titar u organima. Testom antigenske prezentacije in vitro i eksperimentima na kimerama koštane srži miševa divljeg tipa i NKG2D-/- ispitali smo ulogu kostimulacije CD8 limfocita T putem receptora NKG2D nakon infekcije s virusima koji izražavaju NKG2D ligande. Rezultati: MULT1MCMV bio je atenuiran in vivo od strane stanica NK u odraslim i novookoćenim miševima, čak i jače od RAE-1γMCMV-a u određenim eksperimentalnim uvjetima. Unatoč atenuaciji, MUTL1MCMV je zadržao imunogeničnost i inducirao je antigen-specifičan odgovor CD8 limfocita T i protuvirusnu humoralnu imunost sličnih obilježja kao i infekcija MCMV-om i RAE-1γMCMV-om. Potvrdili smo da kostimulacijski signal putem receptora NKG2D pojačava odgovor CD8 limfocita T nakon infekcije s virusima koji izražavaju NKG2D ligande. Zaključak: MULT1MCMV je atenuiran in vivo čak i jače od MCMV-a koji izražava NKG2D ligand slabijeg afiniteta. Također, zadržao je imunogeničnost i potiče zaštitnu stečenu imunost i kao takav pokazuje povoljna obilježja cjepiva.Objectives: NKG2D is an activating receptor on NK cells and costimulatory receptor on T cells. Cellular ligands for this receptor are differentially expressed during the development and in the tissues and have different affinity for the receptor. Human cytomegalovirus (HCMV) is a widely spread herpesvirus which induces unique T cell response characterized by accumulation of virus-specific T cells with effector properties. This feature makes this virus a good vaccine candidate. One of the critical characteristics of every live vaccine is safety, so in our previous research we developed a new approach in designing vaccine based on mouse CMV (MCMV) expressing NKG2D ligand RAE-1γ instead of its viral inhibitor. Since MULT1 is an NKG2D ligand of highest affinity for the receptor, we constructed MCMV expressing this ligand instead of its viral inhibitor (MULT1MCMV) and compared it with RAE-1γMCMV in terms of viral control, immunobiology in vivo and explored their protective capacity as a vaccine. Material and Methods: To examine viral control and immune response to MULT1MCMV in vivo, we infected adult and newborn mice with MCMV, RAE-1γMCMV and MULT1MCMV and followed viral titer in organs of infected animals and did phenotypic analysis of NK cells and CD8 T cells. We tested protective immunity by adoptive transfer of CD8 T cells from immunized mice into naïve recipients which were subsequently infected with MCMV and analyzed viral titer in their organs. By using in vitro antigen presentation assay and bone marrow chimeras of wild type and NKG2D-/- mice we examined the role of NKG2D costimulation on CD8 T cells after infection with recombinant viruses expressing NKG2D ligands. Results: MULT1MCMV was attenuated in vivo by NK cells in NKG2D-dependent manner in both adult and newborn mice, even more strongly than RAE1-γMCMV in certain experimental conditions. Despite attenuation, MULT1MCMV was immunogenic and induced antigen-specific CD8 T cell response and anti-viral humoral response, comparable to infection with MCMV and RAE-1γMCMV. We showed that costimulatory signal via NKG2D receptor on CD8 T cells is able to boost their response after infection with recombinant viruses expressing NKG2D ligands. Conclusion: MULT1MCMV is attenuated in vivo even stronger than MCMV expressing NKG2D ligand of lower affinity, RAE-1γ. Moreover, it retained its immunogenicity and was able to induce protective adaptive immunity and as such shows excellent vaccine properties

ROLE OF NKG2D LIGANDS OF DIFFERENT AFFINITIES IN THE RECOMBINANT MOUSE CYTOMEGALOVIRUS INFECTION AND VACCINE DEVELOPMENT

Cilj istraživanja: NKG2D je aktivacijski receptor na stanicama NK i kostimulacijski receptor na limfocitima T. Stanični ligandi za receptor NKG2D su razvojno i tkivno diferencijalno izražene molekule s različitim afinitetom za isti receptor. Humani citomegalovirus (HCMV) je široko rasprostranjen herpesvirus koji potiče stvaranje svojstvenog odgovora limfocita T karakteriziranog akumulacijom virus-specifičnih stanica efektorskih obilježja što ga čini dobrim kandidatom za razvoj cjepiva. Jedno od nužnih karakteristika svakog živog cjepiva je da bude sigurno za primjenu pa smo u našim prethodnim istraživanjima razvili novi koncept cjepiva na modelu mišjeg CMV-a (MCMV) koji izražava ligand za receptor NKG2D, RAE-1γ (RAE-1γMCMV) umjesto njegovog virusnog inhibitora. Kako je MULT1 mišji NKG2D ligand najjačeg afiniteta za receptor, konstruirali smo rekombinantni MCMV u kojemu je gen za MULT1 umetnut na mjestu njegovog virusnog inhibitora (MULT1MCMV) i komparativnim pristupom smo ispitali imunosni odgovor i imunosnu kontrolu RAE-1γMCMV-a i MULT1MCMV-a in vivo te odredili njihovu sposobnost poticanja zaštitne imunosti. Materijal i metode: Kako bi ispitali kontrolu i imunosni odgovor na MULT1MCMV in vivo, inficirali smo odrasle i novookoćene miševe s MCMV-om, RAE-1γMCMV-om i MULT1MCMV-om te pratili virusni titar u organima inficiranih životinja i fenotipski okarakterizirali stanice NK i CD8 limfocite T. Zaštitnu imunost CD8 limfocita T smo ispitali adoptivnim prijenosom stanica iz imunih životinja u naivne imunokompromitirane primatelje koje smo potom inficirali MCMV-om i pratili virusni titar u organima. Testom antigenske prezentacije in vitro i eksperimentima na kimerama koštane srži miševa divljeg tipa i NKG2D-/- ispitali smo ulogu kostimulacije CD8 limfocita T putem receptora NKG2D nakon infekcije s virusima koji izražavaju NKG2D ligande. Rezultati: MULT1MCMV bio je atenuiran in vivo od strane stanica NK u odraslim i novookoćenim miševima, čak i jače od RAE-1γMCMV-a u određenim eksperimentalnim uvjetima. Unatoč atenuaciji, MUTL1MCMV je zadržao imunogeničnost i inducirao je antigen-specifičan odgovor CD8 limfocita T i protuvirusnu humoralnu imunost sličnih obilježja kao i infekcija MCMV-om i RAE-1γMCMV-om. Potvrdili smo da kostimulacijski signal putem receptora NKG2D pojačava odgovor CD8 limfocita T nakon infekcije s virusima koji izražavaju NKG2D ligande. Zaključak: MULT1MCMV je atenuiran in vivo čak i jače od MCMV-a koji izražava NKG2D ligand slabijeg afiniteta. Također, zadržao je imunogeničnost i potiče zaštitnu stečenu imunost i kao takav pokazuje povoljna obilježja cjepiva.Objectives: NKG2D is an activating receptor on NK cells and costimulatory receptor on T cells. Cellular ligands for this receptor are differentially expressed during the development and in the tissues and have different affinity for the receptor. Human cytomegalovirus (HCMV) is a widely spread herpesvirus which induces unique T cell response characterized by accumulation of virus-specific T cells with effector properties. This feature makes this virus a good vaccine candidate. One of the critical characteristics of every live vaccine is safety, so in our previous research we developed a new approach in designing vaccine based on mouse CMV (MCMV) expressing NKG2D ligand RAE-1γ instead of its viral inhibitor. Since MULT1 is an NKG2D ligand of highest affinity for the receptor, we constructed MCMV expressing this ligand instead of its viral inhibitor (MULT1MCMV) and compared it with RAE-1γMCMV in terms of viral control, immunobiology in vivo and explored their protective capacity as a vaccine. Material and Methods: To examine viral control and immune response to MULT1MCMV in vivo, we infected adult and newborn mice with MCMV, RAE-1γMCMV and MULT1MCMV and followed viral titer in organs of infected animals and did phenotypic analysis of NK cells and CD8 T cells. We tested protective immunity by adoptive transfer of CD8 T cells from immunized mice into naïve recipients which were subsequently infected with MCMV and analyzed viral titer in their organs. By using in vitro antigen presentation assay and bone marrow chimeras of wild type and NKG2D-/- mice we examined the role of NKG2D costimulation on CD8 T cells after infection with recombinant viruses expressing NKG2D ligands. Results: MULT1MCMV was attenuated in vivo by NK cells in NKG2D-dependent manner in both adult and newborn mice, even more strongly than RAE1-γMCMV in certain experimental conditions. Despite attenuation, MULT1MCMV was immunogenic and induced antigen-specific CD8 T cell response and anti-viral humoral response, comparable to infection with MCMV and RAE-1γMCMV. We showed that costimulatory signal via NKG2D receptor on CD8 T cells is able to boost their response after infection with recombinant viruses expressing NKG2D ligands. Conclusion: MULT1MCMV is attenuated in vivo even stronger than MCMV expressing NKG2D ligand of lower affinity, RAE-1γ. Moreover, it retained its immunogenicity and was able to induce protective adaptive immunity and as such shows excellent vaccine properties

Small RNA and Cancer: David vs. Goliath

RNA interference (RNAi) is an epigenetic mechanism involved in regulation of gene expression. It relies on small non-coding RNAs: endogenous miRNA and exogenous siRNA. Among various vital processes in the cell, RNAi regulates the cell cycle progression and apoptosis. Hence, (epi)mutations of the RNAi system can force the cell toward promotion of proliferation and evasion of apoptosis leading to neoplastic transformation. Aberrant RNAi is commonly found in various cancers or even precancerous lesions and seems to be involved in anti-cancer drug resistance as well. Therefore biomedical science nowadays tends to identify RNAi profiles and translate them into clinical biomarkers for cancer diagnostics and therapy response. Since exogenous branch of RNAi pathway sustains specific iatrogenic regulation of gene expression, intense attempts of developing novel anticancer therapy approaches using synthetic small non-coding RNAs are on-going. Several experimental RNAi therapies in different stages of clinical trials are expected to inhibit cell proliferation and re- establish apoptotic activity in transformed cells. In this review we focus on recent discoveries of RNAi regulating apoptosis, enclose these findings in cancer biology context and discuss potential translation of the field into clinical medical practice considering novel trends in management of cancer

Small RNA and Cancer: David vs. Goliath

RNA interference (RNAi) is an epigenetic mechanism involved in regulation of gene expression. It relies on small non-coding RNAs: endogenous miRNA and exogenous siRNA. Among various vital processes in the cell, RNAi regulates the cell cycle progression and apoptosis. Hence, (epi)mutations of the RNAi system can force the cell toward promotion of proliferation and evasion of apoptosis leading to neoplastic transformation. Aberrant RNAi is commonly found in various cancers or even precancerous lesions and seems to be involved in anti-cancer drug resistance as well. Therefore biomedical science nowadays tends to identify RNAi profiles and translate them into clinical biomarkers for cancer diagnostics and therapy response. Since exogenous branch of RNAi pathway sustains specific iatrogenic regulation of gene expression, intense attempts of developing novel anticancer therapy approaches using synthetic small non-coding RNAs are on-going. Several experimental RNAi therapies in different stages of clinical trials are expected to inhibit cell proliferation and re- establish apoptotic activity in transformed cells. In this review we focus on recent discoveries of RNAi regulating apoptosis, enclose these findings in cancer biology context and discuss potential translation of the field into clinical medical practice considering novel trends in management of cancer

Immune responses to congenital cytomegalovirus infection.

Human cytomegalovirus (HCMV) is the most common cause of viral infection acquired in utero. Even though the infection has been studied for several decades, immune determinants important for virus control and mechanisms of long-term sequelae caused by infection are still insufficiently characterized. Animal models of congenital HCMV infection provide unique opportunity to study various aspects of human disease. In this review, we summarize current knowledge on the role of immune system in congenital CMV infection, with emphasis on lessons learned from mouse model of congenital CMV infectio