Background: The increasing incidence of Neurobehavioral Disorders (NBDs), such as Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Developmental Coordination Disorder (DCD), is of major concern in public health. Although early detection of a developing NBD is critical to enable intervention while brain plasticity is prominent, no screening tool for NBD development at infancy is available. The aim here was to assess whether risk factors that predict forthcoming NBDs can be identified at early infancy. Methods: The Israeli Health Organization provides a developmental follow-up system since birth at special well-baby-care clinics (‘Tipat Chalav’). The documented data was used to examine the charts of 161 babies, who later in life (2-10 years of age) were diagnosed for NBDs (47 ASD, 56 DCD, 58 ADHD). Their medical history at 0-18 months of age was compared to that of 58 babies with typical development (control group). Ten covariates including 28 parameters were collected, compared and statistically analysed. Results: This analysis indicated that deviation from trajectories of seven parameters (gestational age, birth weight, head circumference percentile, weight percentile, gross motor development, difficulties in speech and communication) may collectively predict the development of ASD with 85% probability. Deviation from trajectories of the above first five parameters may collectively predict the development of DCD with 72% probability. Early risk factors that may predict ADHD development with 58% probability were previously described (Gurevitz et al 2014). Conclusion: This cohort retrospective study illuminates risk factors at infancy that may predict the development of NBDs. Most prominent are deviations from weight followed by deviations in head circumference trajectories, and delay in motor development due to muscle strength and tone irregularities. Identification of risk factors at infancy is crucial for early intervention programs, such as prevention of rapid changes in weight and manipulations to strengthen motor development and the corresponding neural circuits. The sooner risk factors are recognized, more efficient an early tailored bio-psycho-social treatment might be. Trial registration: Retrospectively registered.
背景:神经行为障碍(nbd)，如自闭症谱系障碍(ASD)、注意缺陷多动障碍(ADHD)和发育协调障碍(DCD)的发病率不断上升，是公共卫生领域关注的主要问题。尽管早期发现发展中的NBD对于在大脑可塑性突出的情况下进行干预至关重要，但目前尚无针对婴儿期NBD发展的筛查工具。这项研究的目的是评估是否可以在婴儿早期识别出预测未来nbd的风险因素。方法:以色列卫生组织在特殊的婴儿保健诊所(“Tipat Chalav”)提供自出生以来的发展随访系统。这些记录在案的数据被用于检查161名婴儿的图表，这些婴儿在生命后期(2-10岁)被诊断为nbd(47名ASD, 56名DCD, 58名ADHD)。将他们0-18月龄的病史与58名发育正常的婴儿(对照组)进行比较。收集10个协变量28个参数进行比较和统计分析。结果:本分析表明，七个参数(胎龄、出生体重、头围百分位数、体重百分位数、大肌肉运动发育、语言和交流困难)偏离轨迹可以共同预测ASD的发展，概率为85%。偏离上述前五个参数的轨迹可以以72%的概率共同预测DCD的发展。早期危险因素预测ADHD发展的概率为58% (Gurevitz et al . 2014)。结论:本队列回顾性研究阐明了婴儿期可能预测nbd发展的危险因素。最突出的是体重的偏离，随后是头围轨迹的偏离，以及由于肌肉力量和音调不规则而导致的运动发育延迟。确定婴儿期的危险因素对于早期干预计划至关重要，例如预防体重的快速变化和加强运动发育和相应神经回路的操作。风险因素越早被发现，早期量身定制的生物心理社会治疗可能就越有效。试验注册:回顾性注册。
{"title":"Early factors at infancy that predict a developing neurobehavioral disorder - A pilot study","authors":"Gurevitz M","doi":"10.15761/jts.1000319","DOIUrl":"https://doi.org/10.15761/jts.1000319","url":null,"abstract":"Background: The increasing incidence of Neurobehavioral Disorders (NBDs), such as Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Developmental Coordination Disorder (DCD), is of major concern in public health. Although early detection of a developing NBD is critical to enable intervention while brain plasticity is prominent, no screening tool for NBD development at infancy is available. The aim here was to assess whether risk factors that predict forthcoming NBDs can be identified at early infancy. Methods: The Israeli Health Organization provides a developmental follow-up system since birth at special well-baby-care clinics (‘Tipat Chalav’). The documented data was used to examine the charts of 161 babies, who later in life (2-10 years of age) were diagnosed for NBDs (47 ASD, 56 DCD, 58 ADHD). Their medical history at 0-18 months of age was compared to that of 58 babies with typical development (control group). Ten covariates including 28 parameters were collected, compared and statistically analysed. Results: This analysis indicated that deviation from trajectories of seven parameters (gestational age, birth weight, head circumference percentile, weight percentile, gross motor development, difficulties in speech and communication) may collectively predict the development of ASD with 85% probability. Deviation from trajectories of the above first five parameters may collectively predict the development of DCD with 72% probability. Early risk factors that may predict ADHD development with 58% probability were previously described (Gurevitz et al 2014). Conclusion: This cohort retrospective study illuminates risk factors at infancy that may predict the development of NBDs. Most prominent are deviations from weight followed by deviations in head circumference trajectories, and delay in motor development due to muscle strength and tone irregularities. Identification of risk factors at infancy is crucial for early intervention programs, such as prevention of rapid changes in weight and manipulations to strengthen motor development and the corresponding neural circuits. The sooner risk factors are recognized, more efficient an early tailored bio-psycho-social treatment might be. Trial registration: Retrospectively registered.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67489527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the last thirty years, improvements in survival rates of oral cancer patients have remained modest, hampered by the late diagnosis of the disease, a lack of understanding of the underlying biology of oral cancer, and a lack of identified actionable targets. While the apical-basal polarity has been widely investigated in normal and pathological contexts, its involvement in oral homeostasis is still not well understood. Here, we discuss the current documented role of PAR-3 complex- dependent apical-basal polarity regulation in oral cancer. We explore molecular switches that link polarity dysfunction to oral cancer initiation and highlight relevant models that would promote our understanding of disease development for therapeutic interventions.
{"title":"The role of apical-basal polarity in oral cancer","authors":"Saintigny P, Bouaoud J, Farrugia G, Darido C","doi":"10.15761/JTS.1000327","DOIUrl":"https://doi.org/10.15761/JTS.1000327","url":null,"abstract":"Over the last thirty years, improvements in survival rates of oral cancer patients have remained modest, hampered by the late diagnosis of the disease, a lack of understanding of the underlying biology of oral cancer, and a lack of identified actionable targets. While the apical-basal polarity has been widely investigated in normal and pathological contexts, its involvement in oral homeostasis is still not well understood. Here, we discuss the current documented role of PAR-3 complex- dependent apical-basal polarity regulation in oral cancer. We explore molecular switches that link polarity dysfunction to oral cancer initiation and highlight relevant models that would promote our understanding of disease development for therapeutic interventions.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67489644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Agrati, Mazzotta, Bordoni, I. Abbate, A. Amendola, S. Notari, F. Forbici, E. Cimini, R. Casetti, M. Capobianchi, M. Bibas, A. Antinori
A 63-years old male was diagnosed for HIV (HIV-RNA undetectable and CD4 T cell count 191/mmc) and HCV active infection (HCV-RNA: 101027 cp/ ml, genotype 1a) in May 2018. In September 2018, the patient presented a bacterial pneumonia with fever, severe leukopenia and thrombocytopenia. HIV-RNA persisted lower than 30 cp/ml and CD4 T cell count was 101/mmc. The severe leukopenia was associated with a general low growth capability of bone marrow derived hematopoietic progenitors and with a low frequency of multipotent lymphoid precursors, suggesting a possible impairment of leukocyte replenishment. T cells were few and dramatically skewed toward an effector profile, suggesting a strongly engaged immune system. Finally, a very high frequency of HIV-specific T cells (3.5 %) showing a polyfunctional profile was found: 70% of HIV specific T cells are able to simultaneously mediate 4 different functions (IFN- γ , TNF- α MIP-1 β , CD107a). In conclusion, we presented a case of one HIV-HCV co-infected patient who, despite an effective immune response able to control HIV replication, showed a progressive disease. The high frequency of polyfunctional CD8 T cells together with a threadbare immune system and with an impaired hematopoiesis may explain the disease progression in the absence of HIV replication.
{"title":"Natural HIV control in a HIV/HCV co-infected patient with a severe leukopenia: A case report","authors":"C. Agrati, Mazzotta, Bordoni, I. Abbate, A. Amendola, S. Notari, F. Forbici, E. Cimini, R. Casetti, M. Capobianchi, M. Bibas, A. Antinori","doi":"10.15761/JTS.1000345","DOIUrl":"https://doi.org/10.15761/JTS.1000345","url":null,"abstract":"A 63-years old male was diagnosed for HIV (HIV-RNA undetectable and CD4 T cell count 191/mmc) and HCV active infection (HCV-RNA: 101027 cp/ ml, genotype 1a) in May 2018. In September 2018, the patient presented a bacterial pneumonia with fever, severe leukopenia and thrombocytopenia. HIV-RNA persisted lower than 30 cp/ml and CD4 T cell count was 101/mmc. The severe leukopenia was associated with a general low growth capability of bone marrow derived hematopoietic progenitors and with a low frequency of multipotent lymphoid precursors, suggesting a possible impairment of leukocyte replenishment. T cells were few and dramatically skewed toward an effector profile, suggesting a strongly engaged immune system. Finally, a very high frequency of HIV-specific T cells (3.5 %) showing a polyfunctional profile was found: 70% of HIV specific T cells are able to simultaneously mediate 4 different functions (IFN- γ , TNF- α MIP-1 β , CD107a). In conclusion, we presented a case of one HIV-HCV co-infected patient who, despite an effective immune response able to control HIV replication, showed a progressive disease. The high frequency of polyfunctional CD8 T cells together with a threadbare immune system and with an impaired hematopoiesis may explain the disease progression in the absence of HIV replication.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67489880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Petiti, M. Dragani, A. Castelli, M. Loiacono, C. Fantino, C. Badino, A. Serra, E. Giugliano, G. Andreani, Rosso, E. Gottardi, G. Rege‐Cambrin, G. Saglio, D. Cilloni, C. Fava
Chronic myeloid leukemia (CML) is characterized by the t(9;22) (q34;q11) translocation which leads to the generation of the BCR-ABL1 protein with constitutive tyrosine kinase activity. BCR-ABL1 is the molecular marker for the evaluation of minimal residual disease (MRD) and its levels throughout the follow up define the depth of molecular remission and guide clinical decisions like change of tyrosine-kinase inhibitor (TKI) or, more recently, discontinuation of therapy [1].
{"title":"Characterization and monitoring by droplet digital PCR of a novel BCR-ABL1 fusion transcript in a patient with chronic myeloid leukemia","authors":"J. Petiti, M. Dragani, A. Castelli, M. Loiacono, C. Fantino, C. Badino, A. Serra, E. Giugliano, G. Andreani, Rosso, E. Gottardi, G. Rege‐Cambrin, G. Saglio, D. Cilloni, C. Fava","doi":"10.15761/JTS.1000369","DOIUrl":"https://doi.org/10.15761/JTS.1000369","url":null,"abstract":"Chronic myeloid leukemia (CML) is characterized by the t(9;22) (q34;q11) translocation which leads to the generation of the BCR-ABL1 protein with constitutive tyrosine kinase activity. BCR-ABL1 is the molecular marker for the evaluation of minimal residual disease (MRD) and its levels throughout the follow up define the depth of molecular remission and guide clinical decisions like change of tyrosine-kinase inhibitor (TKI) or, more recently, discontinuation of therapy [1].","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67490635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zinc is a trace element in the mammalian body, and increasing evidence is suggesting that it plays a critical role in bone development and in the differentiation of bone cells such as osteoblasts, osteoclasts, and chondrocytes. In vivo and in vitro studies have shown that zinc affects osteoclast differentiation. Zinc-sensitive ion channels have been reported. Zinc-related ion channel is ORAI1, which is a store-operated Ca 2+ entry channel subunit, and zinc inhibits the activity of this channel. ORAI1 channels play a significant role in regulating osteoclastic Ca 2+ oscillations during osteoclast differentiation. Knockdown of ORAI1 inhibited osteoclast differentiation. Zinc also inhibited osteoclastogenesis however, its inhibition was reduced by ORAI1 knockdown. Interestingly, zinc can change the osteoclastic membrane potential. Based on this, hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels were investigated and were found to be highly expressed in osteoclasts. High concentrations of zinc chloride increase Ih current which is generated by HCN channels, suggesting a complicated relationship between HCN channels and zinc. Zinc plays various roles in bone physiology through zinc-modulated ion channels. Signaling of these ion channels would be promising targets for treating skeletal diseases. 1200 analog-digital (Axon Instruments), using software (Axon Instruments). Voltage steps (from -30 to −150 mV) at holding
{"title":"Role of zinc and zinc-modulated ion channels, ORAI1 and HCN in osteoclasts","authors":"T. Notomi, Akiko Hiyama, T. Nozaki","doi":"10.15761/JTS.1000359","DOIUrl":"https://doi.org/10.15761/JTS.1000359","url":null,"abstract":"Zinc is a trace element in the mammalian body, and increasing evidence is suggesting that it plays a critical role in bone development and in the differentiation of bone cells such as osteoblasts, osteoclasts, and chondrocytes. In vivo and in vitro studies have shown that zinc affects osteoclast differentiation. Zinc-sensitive ion channels have been reported. Zinc-related ion channel is ORAI1, which is a store-operated Ca 2+ entry channel subunit, and zinc inhibits the activity of this channel. ORAI1 channels play a significant role in regulating osteoclastic Ca 2+ oscillations during osteoclast differentiation. Knockdown of ORAI1 inhibited osteoclast differentiation. Zinc also inhibited osteoclastogenesis however, its inhibition was reduced by ORAI1 knockdown. Interestingly, zinc can change the osteoclastic membrane potential. Based on this, hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels were investigated and were found to be highly expressed in osteoclasts. High concentrations of zinc chloride increase Ih current which is generated by HCN channels, suggesting a complicated relationship between HCN channels and zinc. Zinc plays various roles in bone physiology through zinc-modulated ion channels. Signaling of these ion channels would be promising targets for treating skeletal diseases. 1200 analog-digital (Axon Instruments), using software (Axon Instruments). Voltage steps (from -30 to −150 mV) at holding","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67490995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. Calvete, S. Mourón, A. Barroso, Nora E. Soberón, M. Blasco, M. Quintela-Fandino, J. Benítez
Telomeres play an important role in various cancer types, where gradual telomere shortening associated with mitotic division leads to cell senescence and apoptosis in early steps of transformation [1]. Abnormal telomere length (TL) may have prognostic significance of malignancy and cancer risk. There is growing evidence from cancer susceptibility and population studies that points to a correlation between genetic variants that shorten TL and an increased risk of cancer [2]. By contrast, reduced telomere shortening induced by mutations in the POT1 gene, encoding a member of the shelterin complex involved in telomere maintenance, lead to long telomeres and tumour progression in several cancer types such as chronic lymphocytic leukaemia, colorectal cancer, melanoma, glioma and angiosarcoma [3]. In breast cancer, TL has been frequently evaluated but previous studies did not establish robust prognostic and/or predictive correlations between TL and any of the three main molecular subtypes [4]. Previously, short but not long telomeres were suggested to be associated with more aggressive breast cancer subtypes [5]. TL does not seem to be associated with increased breast cancer risk either [6,7]. Lack of significant evidence can be explained by the recent observation that chemotherapy affects TL [8]. Thus, treatment-naïve patients should be considered in the studies that aim to correlate TL with disease susceptibility or clinical course, since chemotherapy-modified TL can bias the true biological associations.
{"title":"Long telomeres: A new prognostic factor for severity in triple-negative breast cancer patients","authors":"O. Calvete, S. Mourón, A. Barroso, Nora E. Soberón, M. Blasco, M. Quintela-Fandino, J. Benítez","doi":"10.15761/jts.1000432","DOIUrl":"https://doi.org/10.15761/jts.1000432","url":null,"abstract":"Telomeres play an important role in various cancer types, where gradual telomere shortening associated with mitotic division leads to cell senescence and apoptosis in early steps of transformation [1]. Abnormal telomere length (TL) may have prognostic significance of malignancy and cancer risk. There is growing evidence from cancer susceptibility and population studies that points to a correlation between genetic variants that shorten TL and an increased risk of cancer [2]. By contrast, reduced telomere shortening induced by mutations in the POT1 gene, encoding a member of the shelterin complex involved in telomere maintenance, lead to long telomeres and tumour progression in several cancer types such as chronic lymphocytic leukaemia, colorectal cancer, melanoma, glioma and angiosarcoma [3]. In breast cancer, TL has been frequently evaluated but previous studies did not establish robust prognostic and/or predictive correlations between TL and any of the three main molecular subtypes [4]. Previously, short but not long telomeres were suggested to be associated with more aggressive breast cancer subtypes [5]. TL does not seem to be associated with increased breast cancer risk either [6,7]. Lack of significant evidence can be explained by the recent observation that chemotherapy affects TL [8]. Thus, treatment-naïve patients should be considered in the studies that aim to correlate TL with disease susceptibility or clinical course, since chemotherapy-modified TL can bias the true biological associations.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67492648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
For the first time the intracranial pressure (ICP) in humans was recorded as pulsatile curve by Giacomini and Mosso in 37-year-old woman with syphilitic infection in 1876 [1]. Nowadays, ICP recording is widely used in neurosurgery and neurointensive units. Although the intraventricular pressure monitoring is the “gold standard”, there are some indirect and non-invasive routes to estimate the value of the intracranial pressure. The main alternative methods are: visual evoked potentials, phase-contrast magnetic resonance, transcranial Doppler, tympanic membrane displacement, intraocular pressure and acoustoelasticity.
{"title":"The osmotic concept of the intracranial pressure","authors":"L. Herbowski","doi":"10.15761/JTS.1000336","DOIUrl":"https://doi.org/10.15761/JTS.1000336","url":null,"abstract":"For the first time the intracranial pressure (ICP) in humans was recorded as pulsatile curve by Giacomini and Mosso in 37-year-old woman with syphilitic infection in 1876 [1]. Nowadays, ICP recording is widely used in neurosurgery and neurointensive units. Although the intraventricular pressure monitoring is the “gold standard”, there are some indirect and non-invasive routes to estimate the value of the intracranial pressure. The main alternative methods are: visual evoked potentials, phase-contrast magnetic resonance, transcranial Doppler, tympanic membrane displacement, intraocular pressure and acoustoelasticity.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67489982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Boutsikou, Adamantia Krepi, Z. Iliodromiti, Eleni Karapati, R. Sokou, N. Iacovidou
Congenital depression of the neonatal skull is a rare entity. Most of the cases have been attributed to obstetric trauma, mainly due to use of forceps, while the minority of cases occurs from intrauterine moulding of the fetal skull due to pressure against maternal bone structures. In the majority of uncomplicated depressions there is gradual resolution, although surgical intervention has also been reported in the literature. We present the case of a term infant born by cesarean section presenting with a skull deformity of the right parietal- occipital area with no accompanying fracture that gradually resolved within 18 months with no neurologic sequelae.
{"title":"Congenital skull deformity of the right parietal-occipital area in a term neonate: A case report","authors":"T. Boutsikou, Adamantia Krepi, Z. Iliodromiti, Eleni Karapati, R. Sokou, N. Iacovidou","doi":"10.15761/jts.1000426","DOIUrl":"https://doi.org/10.15761/jts.1000426","url":null,"abstract":"Congenital depression of the neonatal skull is a rare entity. Most of the cases have been attributed to obstetric trauma, mainly due to use of forceps, while the minority of cases occurs from intrauterine moulding of the fetal skull due to pressure against maternal bone structures. In the majority of uncomplicated depressions there is gradual resolution, although surgical intervention has also been reported in the literature. We present the case of a term infant born by cesarean section presenting with a skull deformity of the right parietal- occipital area with no accompanying fracture that gradually resolved within 18 months with no neurologic sequelae.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67492889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Donetti, G. Lombardo, F. B. Preis, L. Cornaghi, L. Pescitelli, F. Prignano
Epidermal cells, together with different molecules of the immunosystem, promote psoriasis, but several data concerning the early phases of this disease still lack. This study evaluated the early morphological features of psoriasis using an organotypic culture of normal human skin. Cellular proliferation, expressions of Toll-like receptors (TLR) 7 and 9, and keratin 17 were analysed by indirect immunofluorescence in normal human skin biopsies exposed to a cytokine mix strictly reproducing a psoriatic environment. After mix incubation, an early and progressive decrease of cell proliferation was detected. TLR9 was present in the granular layer of mix samples, while TLR7 was expressed throughout the entire epidermal compartment. K17 expression was evident after mix exposure. In conclusion, our results prove that a psoriatic microenvironment is able to induce pivotal morphological changes in our skin model, strongly suggesting that an early epidermal “psoriatic switch” can be reproduced for studying the epidermal homeostasis and innate immune response.
{"title":"3D skin model to investigate the early epidermal morphological psoriatic features","authors":"E. Donetti, G. Lombardo, F. B. Preis, L. Cornaghi, L. Pescitelli, F. Prignano","doi":"10.15761/JTS.1000361","DOIUrl":"https://doi.org/10.15761/JTS.1000361","url":null,"abstract":"Epidermal cells, together with different molecules of the immunosystem, promote psoriasis, but several data concerning the early phases of this disease still lack. This study evaluated the early morphological features of psoriasis using an organotypic culture of normal human skin. Cellular proliferation, expressions of Toll-like receptors (TLR) 7 and 9, and keratin 17 were analysed by indirect immunofluorescence in normal human skin biopsies exposed to a cytokine mix strictly reproducing a psoriatic environment. After mix incubation, an early and progressive decrease of cell proliferation was detected. TLR9 was present in the granular layer of mix samples, while TLR7 was expressed throughout the entire epidermal compartment. K17 expression was evident after mix exposure. In conclusion, our results prove that a psoriatic microenvironment is able to induce pivotal morphological changes in our skin model, strongly suggesting that an early epidermal “psoriatic switch” can be reproduced for studying the epidermal homeostasis and innate immune response.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49082460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-04-01Epub Date: 2018-10-01DOI: 10.15761/JTS.1000282
B Nandi, S Talluri, S Kumar, C Yenumula, J S Gold, R Prabhala, N C Munshi, M A Shammas
A variety of factors, whether extracellular (mutagens/carcinogens and viruses in the environment, chronic inflammation and radiation associated with the environment and/or electronic devices/machines) and/or intracellular (oxidative metabolites of food, oxidative stress due to inflammation, acid production, replication stress, DNA replication/repair errors, and certain hormones, cytokines, growth factors), pose a constant threat to the genomic integrity of a living cell. However, in the normal cellular environment multiple biological pathways including DNA repair, cell cycle, apoptosis and the immune system work in a precise, regulated (tightly controlled), timely and concerted manner to ensure genomic integrity, stability and proper functioning of a cell. If damage to DNA takes place, it is efficiently and accurately repaired by the DNA repair systems. Homologous recombination (HR) which utilizes either a homologous chromosome (in G1 phase) or a sister chromatid (in G2) as a template to repair the damage, is known to be the most precise repair system. HR in G2 which utilizes a sister chromatid as a template is also called an error free repair system. If DNA damage in a cell is so extensive that it overwhelms the repair system/s, the cell is eliminated by apoptosis. Thus, multiple pathways ensure that genome of a cell is intact and stable. However, constant exposure to DNA damage and/or dysregulation of DNA repair mechanism/s poses a risk of mutation and cancer. Oncogenesis, which seems to be a multistep process, is associated with acquisition of a number of genomic changes that enable a normal cell to progress from benign to malignant transformation. Transformed/cancer cells are recognized and killed by the immune system. However, the ongoing acquisition of new genomic changes enables cancer cells to survive/escape immune attack, evolve into a more aggressive phenotype, and eventually develop resistance to therapy. Although DNA repair (especially the HR) and the immune system play unique roles in preserving genomic integrity of a cell, they can also contribute to DNA damage, genomic instability and oncogenesis. The purpose of this article is to highlight the roles of DNA repair (especially HR) and the immune system in genomic evolution, with special focus on gastrointestinal cancer.
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