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Article ; Online: Immune Checkpoint molecules in solid organ transplantation: a promising way to prevent rejection.

Righi, Ilaria / Trabattoni, Daria / Rosso, Lorenzo / Vaira, Valentina / Clerici, Mario

2024 , Page(s) 106860

Abstract: Immune checkpoint (IC) molecules modulate immune responses upon antigen presentation; the interaction between different IC molecules will result in the stimulation or, rather, the thwarting of such responses. Tumor cells express increased amounts of ... ...

Abstract	Immune checkpoint (IC) molecules modulate immune responses upon antigen presentation; the interaction between different IC molecules will result in the stimulation or, rather, the thwarting of such responses. Tumor cells express increased amounts of inhibitory IC molecules in an attempt to evade immune responses; therapeutic agents have been developed that bind inhibitory IC molecules, restoring tumor-directed immune responses and changing the prognosis of a number of cancers. Stimulation of inhibitory IC molecules could be beneficial in preventing rejection in the setting of solid organ transplantation (SOT), and in vivo as well as in vivo results obtained in animal models show this to indeed to be the case. With the exception of belatacept, a monoclonal antibody (mAb) in which an IgG Fc fragment is linked to the extracellular domain of CTLA-4, this has not yet translated into the generation of novel therapeutic approaches to prevent SOT rejection. We provide a review of state-of-the art knowledge on the role played by IC molecules in transplantation, confident that innovative research will lead to new avenues to manage rejection in solid organ transplant.
Language	English
Publishing date	2024-04-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	445150-8
ISSN	1879-0542 ; 0165-2478
ISSN (online)	1879-0542
ISSN	0165-2478
DOI	10.1016/j.imlet.2024.106860
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Article ; Online: Living With Chronic HIV Disease in the Antiretroviral Era: The Impact of Neurocognitive Impairment on Everyday Life Functions.

Ripamonti, Enrico / Clerici, Mario

Topics in antiviral medicine

2021 Volume 29, Issue 3, Page(s) 386–396

Abstract: Although there is extensive literature around the biologic correlations of neurocognitive function in HIV/AIDS, less is known about the impact in everyday living. We conducted a systematic review of the association of neurocognitive impairment with ... ...

Abstract	Although there is extensive literature around the biologic correlations of neurocognitive function in HIV/AIDS, less is known about the impact in everyday living. We conducted a systematic review of the association of neurocognitive impairment with everyday life functions in people with HIV on antiretroviral therapy. We specifically focused on attention, executive function, processing speed, and the central executive component of the working memory. We considered 3 domains of everyday functions: (1) autonomy, (2) decision making and adherence to treatment, and (3) quality of life and psychologic wellbeing. The relationship between neurocognitive impairment and mental health was examined, given its correlation with everyday life functions. Results indicate that people with HIV do experience problems with autonomy of daily living (especially if aged older than 50 years) and with decision making, and neurocognitive impairment plays a role in this regard. Psychologic wellbeing is associated with executive function and processing speed. These patients may also have a reduced quality of life, but the relationship between quality of life and cognition is uncertain or could be mediated by other factors. Neurocognitive impairment correlates with depression and anxiety; however, the relationship of cognitive performance with apathy is still controversial.
MeSH term(s)	Aged ; Anti-Retroviral Agents/therapeutic use ; Cognition ; Executive Function ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Quality of Life
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2021-08-09
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	2656632-1
ISSN	2161-5853 ; 2161-5853
ISSN (online)	2161-5853
ISSN	2161-5853
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Article ; Online: Extracellular Vesicles as Biomarkers for Parkinson's Disease: How Far from Clinical Translation?

Gualerzi, Alice / Picciolini, Silvia / Bedoni, Marzia / Guerini, Franca Rosa / Clerici, Mario / Agliardi, Cristina

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder affecting about 10 million people worldwide with a prevalence of about 2% in the over-80 population. The disease brings in also a huge annual economic burden, recently estimated by the Michael J ... ...

Abstract	Parkinson's disease (PD) is a neurodegenerative disorder affecting about 10 million people worldwide with a prevalence of about 2% in the over-80 population. The disease brings in also a huge annual economic burden, recently estimated by the Michael J Fox Foundation for Parkinson's Research to be USD 52 billion in the United States alone. Currently, no effective cure exists, but available PD medical treatments are based on symptomatic prescriptions that include drugs, surgical approaches and rehabilitation treatment. Due to the complex biology of a PD brain, the design of clinical trials and the personalization of treatment strategies require the identification of accessible and measurable biomarkers to monitor the events induced by treatment and disease progression and to predict patients' responsiveness. In the present review, we strive to briefly summarize current knowledge about PD biomarkers, focusing on the role of extracellular vesicles as active or involuntary carriers of disease-associated proteins, with particular attention to those research works that envision possible clinical applications.
MeSH term(s)	Humans ; Parkinson Disease/diagnosis ; Extracellular Vesicles ; Biomarkers ; Brain ; Disease Progression
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-01-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25021136
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Article ; Online: Analysis of variola virus molecular evolution suggests an old origin of the virus consistent with historical records.

Forni, Diego / Molteni, Cristian / Cagliani, Rachele / Clerici, Mario / Sironi, Manuela

Microbial genomics

2023 Volume 9, Issue 1

Abstract: Archaeovirology efforts provided a rich portrait of the evolutionary history of variola virus (VARV, the cause of smallpox), which was characterized by lineage extinctions and a relatively recent origin of the virus as a human pathogen (~1700 years ago, ... ...

Abstract	Archaeovirology efforts provided a rich portrait of the evolutionary history of variola virus (VARV, the cause of smallpox), which was characterized by lineage extinctions and a relatively recent origin of the virus as a human pathogen (~1700 years ago, ya). This contrasts with historical records suggesting the presence of smallpox as early as 3500 ya. By performing an analysis of ancestry components in modern, historic, and ancient genomes, we unveil the progressive drifting of VARV lineages from a common ancestral population and we show that a small proportion of Viking Age ancestry persisted until the 18th century. After the split of the P-I and P-II lineages, the former experienced a severe bottleneck. With respect to the emergence of VARV as a human pathogen, we revise time estimates by accounting for the time-dependent rate phenomenon. We thus estimate that VARV emerged earlier than 3800 ya, supporting its presence in ancient societies, as pockmarked Egyptian mummies suggest.
MeSH term(s)	Humans ; Variola virus/genetics ; Smallpox/epidemiology ; Smallpox/history ; Phylogeny ; Genome, Viral/genetics ; Evolution, Molecular
Language	English
Publishing date	2023-02-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2835258-0
ISSN	2057-5858 ; 2057-5858
ISSN (online)	2057-5858
ISSN	2057-5858
DOI	10.1099/mgen.0.000932
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Article ; Online: The role of endoplasmic reticulum aminopeptidases in type 1 diabetes mellitus.

Limanaqi, Fiona / Vicentini, Chiara / Saulle, Irma / Clerici, Mario / Biasin, Mara

Life sciences

2023 Volume 323, Page(s) 121701

Abstract: Type-I diabetes mellitus (T1DM) is generally considered as a chronic, T-cell mediated autoimmune disease. This notwithstanding, both the endogenous characteristics of β-cells, and their response to environmental factors and exogenous inflammatory stimuli ...

Abstract	Type-I diabetes mellitus (T1DM) is generally considered as a chronic, T-cell mediated autoimmune disease. This notwithstanding, both the endogenous characteristics of β-cells, and their response to environmental factors and exogenous inflammatory stimuli are key events in disease progression and exacerbation. As such, T1DM is now recognized as a multifactorial condition, with its onset being influenced by both genetic predisposition and environmental factors, among which, viral infections represent major triggers. In this frame, endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) hold center stage. ERAPs represent the main hydrolytic enzymes specialized in trimming of N-terminal antigen peptides to be bound by MHC class I molecules and presented to CD8+ T cells. Thus, abnormalities in ERAPs expression alter the peptide-MHC-I repertoire both quantitatively and qualitatively, fostering both autoimmune and infectious diseases. Although only a few studies succeeded in determining direct associations between ERAPs variants and T1DM susceptibility/outbreak, alterations of ERAPs do impinge on a plethora of biological events which might indeed contribute to the disease development/exacerbation. Beyond abnormal self-antigen peptide trimming, these include preproinsulin processing, nitric oxide (NO) production, ER stress, cytokine responsiveness, and immune cell recruitment/activity. The present review brings together direct and indirect evidence focused on the immunobiological role of ERAPs in T1DM onset and progression, covering both genetic and environmental aspects.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/metabolism ; Aminopeptidases/genetics ; Aminopeptidases/metabolism ; Histocompatibility Antigens Class I/metabolism ; Peptides/chemistry ; Endoplasmic Reticulum/metabolism ; Minor Histocompatibility Antigens/metabolism
Chemical Substances	Aminopeptidases (EC 3.4.11.-) ; Histocompatibility Antigens Class I ; Peptides ; Minor Histocompatibility Antigens ; ERAP1 protein, human (EC 3.4.11.-) ; ERAP2 protein, human (EC 3.4.11.-)
Language	English
Publishing date	2023-04-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121701
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Article ; Online: Dinucleotide biases in RNA viruses that infect vertebrates or invertebrates.

Forni, Diego / Pozzoli, Uberto / Cagliani, Rachele / Clerici, Mario / Sironi, Manuela

Microbiology spectrum

2023 Volume 11, Issue 6, Page(s) e0252923

Abstract: Importance: Akin to a molecular signature, dinucleotide composition can be exploited by the zinc-finger antiviral protein (ZAP) to restrict CpG-rich (and UpA-rich) RNA viruses. ZAP evolved in tetrapods, and it is not encoded by invertebrates and fish. ... ...

Abstract	Importance: Akin to a molecular signature, dinucleotide composition can be exploited by the zinc-finger antiviral protein (ZAP) to restrict CpG-rich (and UpA-rich) RNA viruses. ZAP evolved in tetrapods, and it is not encoded by invertebrates and fish. Because a systematic analysis is missing, we analyzed the genomes of RNA viruses that infect vertebrates or invertebrates. We show that vertebrate single-stranded (ss) RNA(+) viruses and, to a lesser extent, double-stranded RNA viruses tend to have stronger CpG bias than invertebrate viruses. Conversely, ssRNA(-) viruses have similar dinucleotide composition whether they infect vertebrates or invertebrates. Analysis of ssRNA(+) viruses that infect mammals, reptiles, and fish indicated that ZAP is unlikely to be a major driver of CpG depletion. We also show that, compared to other coronaviruses, the genome of SARS-CoV-2 is not homogeneously CpG-depleted. Our study provides new insights into virus evolution and strategies for recoding RNA virus genomes.
MeSH term(s)	Animals ; RNA Viruses/genetics ; Invertebrates/genetics ; Vertebrates/genetics ; SARS-CoV-2/genetics ; RNA ; Mammals
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02529-23
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Article ; Online: Disease-causing human viruses: novelty and legacy.

Forni, Diego / Cagliani, Rachele / Clerici, Mario / Sironi, Manuela

Trends in microbiology

2022 Volume 30, Issue 12, Page(s) 1232–1242

Abstract: About 270 viruses are known to infect humans. Some of these viruses have been known for centuries, whereas others have recently emerged. During their evolutionary history, humans have moved out of Africa to populate the world. In historical times, human ... ...

Abstract	About 270 viruses are known to infect humans. Some of these viruses have been known for centuries, whereas others have recently emerged. During their evolutionary history, humans have moved out of Africa to populate the world. In historical times, human migrations resulted in the displacement of large numbers of people. All these events determined the movement and dispersal of human-infecting viruses. Technological advances have resulted in the characterization of the genetic variability of human viruses, both in extant and in archaeological samples. Field studies investigated the diversity of viruses hosted by other animals. In turn, these advances provided insight into the evolutionary history of human viruses back in time and defined the key events through which they originated and spread.
MeSH term(s)	Animals ; Humans ; Biological Evolution ; Viruses/genetics ; Africa ; Phylogeny
Language	English
Publishing date	2022-07-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2022.07.002
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Article: Disease-causing human viruses: novelty and legacy

Forni, Diego / Cagliani, Rachele / Clerici, Mario / Sironi, Manuela

Trends in microbiology. 2022,

2022

Abstract	About 270 viruses are known to infect humans. Some of these viruses have been known for centuries, whereas others have recently emerged. During their evolutionary history, humans have moved out of Africa to populate the world. In historical times, human migrations resulted in the displacement of large numbers of people. All these events determined the movement and dispersal of human-infecting viruses. Technological advances have resulted in the characterization of the genetic variability of human viruses, both in extant and in archaeological samples. Field studies investigated the diversity of viruses hosted by other animals. In turn, these advances provided insight into the evolutionary history of human viruses back in time and defined the key events through which they originated and spread.
Keywords	archaeology ; genetic variation ; humans ; people ; Africa
Language	English
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2022.07.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: VDR Gene Single Nucleotide Polymorphisms and Autoimmunity: A Narrative Review

Agliardi, Cristina / Guerini, Franca Rosa / Bolognesi, Elisabetta / Zanzottera, Milena / Clerici, Mario

Biology (Basel). 2023 June 26, v. 12, no. 7

2023

Abstract: The vitamin D/Vitamin D receptor (VDR) axis is crucial for human health as it regulates the expression of genes involved in different functions, including calcium homeostasis, energy metabolism, cell growth and differentiation, and immune responses. In ... ...

Abstract	The vitamin D/Vitamin D receptor (VDR) axis is crucial for human health as it regulates the expression of genes involved in different functions, including calcium homeostasis, energy metabolism, cell growth and differentiation, and immune responses. In particular, the vitamin D/VDR complex regulates genes of both innate and adaptive immunity. Autoimmune diseases are believed to arise from a genetic predisposition and the presence of triggers such as hormones and environmental factors. Among these, a role for Vitamin D and molecules correlated to its functions has been repeatedly suggested. Four single nucleotide polymorphisms (SNPs) of the VDR gene, ApaI, BsmI, TaqI, and FokI, in particular, have been associated with autoimmune disorders. The presence of particular VDR SNP alleles and genotypes, thus, was observed to modulate the likelihood of developing diverse autoimmune conditions, either increasing or reducing it. In this work, we will review the scientific literature suggesting a role for these different factors in the pathogenesis of autoimmune conditions and summarize evidence indicating a possible VDR SNP involvement in the onset of these diseases. A better understanding of the role of the molecular mechanisms linking Vitamin D/VDR and autoimmunity might be extremely useful in designing novel therapeutic avenues for these disorders.
Keywords	adaptive immunity ; autoimmunity ; calcium ; cell growth ; energy metabolism ; genes ; genetic predisposition to disease ; homeostasis ; human health ; pathogenesis ; therapeutics
Language	English
Dates of publication	2023-0626
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12070916
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The role of endoplasmic reticulum aminopeptidases in type 1 diabetes mellitus

Limanaqi, Fiona / Vicentini, Chiara / Saulle, Irma / Clerici, Mario / Biasin, Mara

Life Sciences. 2023 June, v. 323 p.121701-

2023

Abstract	Type-I diabetes mellitus (T1DM) is generally considered as a chronic, T-cell mediated autoimmune disease. This notwithstanding, both the endogenous characteristics of β-cells, and their response to environmental factors and exogenous inflammatory stimuli are key events in disease progression and exacerbation. As such, T1DM is now recognized as a multifactorial condition, with its onset being influenced by both genetic predisposition and environmental factors, among which, viral infections represent major triggers. In this frame, endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) hold center stage. ERAPs represent the main hydrolytic enzymes specialized in trimming of N-terminal antigen peptides to be bound by MHC class I molecules and presented to CD8+ T cells. Thus, abnormalities in ERAPs expression alter the peptide-MHC-I repertoire both quantitatively and qualitatively, fostering both autoimmune and infectious diseases. Although only a few studies succeeded in determining direct associations between ERAPs variants and T1DM susceptibility/outbreak, alterations of ERAPs do impinge on a plethora of biological events which might indeed contribute to the disease development/exacerbation. Beyond abnormal self-antigen peptide trimming, these include preproinsulin processing, nitric oxide (NO) production, ER stress, cytokine responsiveness, and immune cell recruitment/activity. The present review brings together direct and indirect evidence focused on the immunobiological role of ERAPs in T1DM onset and progression, covering both genetic and environmental aspects.
Keywords	T-lymphocytes ; aminopeptidases ; antigens ; autoimmune diseases ; cytokines ; disease progression ; endoplasmic reticulum ; genetic predisposition to disease ; insulin-dependent diabetes mellitus ; nitric oxide ; ERAP1 ; ERAP2 ; MHC-I ; Pancreatic β-cell ; ER stress ; Preproinsulin ; Viral infections
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121701
Database	NAL-Catalogue (AGRICOLA)

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