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1.
Infectio ; 25(4): 300-302, oct.-dic. 2021.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1286727

RESUMO

Resumen Caso reporte de una enfermedad infrecuente, aproximadamente 1% de las artritis sépticas son esternoclavicular, con poca respuesta a antibioterapia intravenosa, requiriendo manejo quirúrgico agresivo, el siguiente caso narra la excelente respuesta con el uso de perlas de sulfato de calcio impregnadas con antibióticos, existiendo en la literatura sólo casos reportes sobre su uso.


Abstract Case report of an infrequent disease, approximately 1% of septic arthritis are sternoclavicular, with little response to intravenous antibiotic therapy, requiring ag gressive surgical management, the following case narrates the excellent response with the use of calcium sulfate pearls impregnated with antibiotics, existing in the literature only cases reports on its use.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Osteomielite , Sulfato de Cálcio , Artrite Infecciosa , Doença
4.
Science ; 373(6562): 1458-1459, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34554809
5.
J Genet ; 1002021.
Artigo em Inglês | MEDLINE | ID: mdl-34553695

RESUMO

X-chromosome inactivation (XCI) is a process involved in the pathogenesis of several diseases. In this mini review, we discuss the known mechanisms associated with XCI, when and how does it initiate, spreads and maintain, as well as the mechanisms that allow some genes to escape from it. We address the skewed XCI, condition in which the process are not fully randomized and its consequences to the phenotype of some pathologies. We debate about the known pathologies implicated, including X unbalanced rearrangements, X-autosomal balanced translocations, Turner and Klinefelter syndromes and also for X-linked diseases and its consequences in males and females. Some pathologies are discussed more in detail such as intellectual disability with a recognized relationship with XCI. Finally, possible future implications of genomic therapy and treatment of patients and list of areas that need further research on this topic are addressed.


Assuntos
Cromossomos Humanos X/genética , Doença/genética , Inativação do Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos
6.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576125

RESUMO

Molecular mechanisms of human disease progression often have complex genetic underpinnings, and sophisticated sequencing approaches coupled with advanced analytics [...].


Assuntos
Biologia Computacional , Doença/genética , Genética Médica , Genômica , Animais , Modelos Animais de Doenças , Redes Reguladoras de Genes , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
7.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502326

RESUMO

The focus of pathology as a biomedical discipline is the identification of the pathomechanisms of diseases and the integration of this knowledge into routine diagnosis and classification. Standard tools are macroscopic and microscopic analysis complemented by immunohistochemistry and molecular pathology. So far, classification has been based on the paradigm of cellular pathology established by Rudolf Virchow and others more than 150 years ago, stating that diseases originate from diseased cells. This dogma is meanwhile challenged by the fact that cells can be fully reprogrammed. Many diseases are nowadays considered to originate from undifferentiated stem cells, induced into a diseased state by genetic or epigenetic alterations. In addition, the completion of the Human Genome Project, with the identification of more than 20.000 genes and a much higher number of gene variants and mutations, led to the concept that diseases are dominated by genetics/epigenetics rather than cells of origin. The axiom of cellular pathology, however, still holds true, as cells are the smallest animate units from which diseases originate. Medical doctors and researchers nowadays have to deal with a tremendous amount of data. The International Classification of Diseases will expand from 14.400 entities/codes in ICD-10 to more than 55.000 in ICD-11. In addition, large datasets generated by "genomics", e.g., whole-genome sequencing, expression profiling or methylome analysis, are meanwhile not only applied in research but also introduced into clinical settings. It constitutes a major task to incorporate all the data into routine medical work. Pathway pathology may help solve this problem. It is based on the realization that diseases are characterized by three essential components: (i) cells of origin/cellular context and (ii) the alteration of cellular as well as (iii) molecular/signal transduction pathways. The concept is illustrated by elaborating on two key cellular pathways, i.e., the cellular senescence of normal cells and the immortality of cancer cells, and by contrasting single cell/single pathway diseases, such as mycoplasma and coughing pneumonia, with complex diseases such as cancer, with multiple cell types as well as multiple affected cellular and signaling pathways. Importantly, the concept of pathway pathology is not just intended to classify disease, but also to conceive new treatment modalities. This article is dedicated to Dr. Leonard Hayflick, who made basic discoveries in pathway pathology not only by identifying cells causing disease (Mycoplasma pneumoniae) and establishing cell strains for treating disease (WI-38 for viral vaccines), but also by first describing cellular senescence and immortality.


Assuntos
Doença/genética , Genoma Humano , Terapia de Alvo Molecular , Medicina de Precisão , Transdução de Sinais , Humanos
8.
Molecules ; 26(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443625

RESUMO

Black garlic (BG) is a form of aged garlic obtained from raw garlic (Allium sativum) via Millard reaction under high temperature (60-90 °C) and humidity (70-90%) for a period of time. Several studies reported higher contents of water-soluble antioxidants compounds (S-allyl cysteine, S-allyl-mercapto cysteine), 5-hydroxymethylfurfural, organosulfur compounds, polyphenol, volatile compounds, and products of other Millard reactions compared to fresh garlic after the thermal processing. Recent studies have demonstrated that BG and its bioactive compounds possess a wide range of biological activities and pharmacological properties that preserve and show better efficacy in preventing different types of diseases. Most of these benefits can be attributed to its anti-oxidation, anti-inflammation, anti-obesity, hepatoprotection, hypolipidemia, anti-cancer, anti-allergy, immunomodulation, nephroprotection, cardiovascular protection, and neuroprotection. Substantial studies have been conducted on BG and its components against different common human diseases in the last few decades. Still, a lot of research is ongoing to find out the therapeutic effects of BG. Thus, in this review, we summarized the pre-clinical and clinical studies of BG and its bioactive compounds on human health along with diverse bioactivity, a related mode of action, and also future challenges.


Assuntos
Doença , Alho/química , Saúde , Manipulação de Alimentos , Humanos
9.
Nature ; 596(7871): 211-220, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34381231

RESUMO

Deciphering the principles and mechanisms by which gene activity orchestrates complex cellular arrangements in multicellular organisms has far-reaching implications for research in the life sciences. Recent technological advances in next-generation sequencing- and imaging-based approaches have established the power of spatial transcriptomics to measure expression levels of all or most genes systematically throughout tissue space, and have been adopted to generate biological insights in neuroscience, development and plant biology as well as to investigate a range of disease contexts, including cancer. Similar to datasets made possible by genomic sequencing and population health surveys, the large-scale atlases generated by this technology lend themselves to exploratory data analysis for hypothesis generation. Here we review spatial transcriptomic technologies and describe the repertoire of operations available for paths of analysis of the resulting data. Spatial transcriptomics can also be deployed for hypothesis testing using experimental designs that compare time points or conditions-including genetic or environmental perturbations. Finally, spatial transcriptomic data are naturally amenable to integration with other data modalities, providing an expandable framework for insight into tissue organization.


Assuntos
Perfilação da Expressão Gênica/métodos , Especificidade de Órgãos/genética , Transcriptoma , Animais , Análise de Dados , Doença/genética , Humanos , Transcrição Genética/genética
10.
Nature ; 596(7870): 43-53, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34349292

RESUMO

The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile genetic elements that can move from one genomic location to another; in this process, they amplify and increase their presence in genomes, sometimes to very high copy numbers. In this Review we discuss new evidence and ideas that the activity of retrotransposons, a major subgroup of transposons overall, influences and even promotes the process of ageing and age-related diseases in complex metazoan organisms, including humans. Retrotransposons have been coevolving with their host genomes since the dawn of life. This relationship has been largely competitive, and transposons have earned epithets such as 'junk DNA' and 'molecular parasites'. Much of our knowledge of the evolution of retrotransposons reflects their activity in the germline and is evident from genome sequence data. Recent research has provided a wealth of information on the activity of retrotransposons in somatic tissues during an individual lifespan, the molecular mechanisms that underlie this activity, and the manner in which these processes intersect with our own physiology, health and well-being.


Assuntos
Envelhecimento/genética , Envelhecimento/patologia , Doença/genética , Retroelementos/genética , Animais , Dano ao DNA , Inativação Gênica , Genoma Humano/genética , Genômica , Humanos , Imunidade Inata
11.
Trends Immunol ; 42(9): 764-781, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34384709

RESUMO

The membrane-spanning 4A (MS4A) family includes 18 members with a tetraspan structure in humans. They are differentially and selectively expressed in immunocompetent cells, such as B cells (CD20/MS4A1) and macrophages (MS4A4A), and associate with, and modulate the signaling activity of, different classes of immunoreceptor, including pattern recognition receptors (PRRs) and Ig receptors. Evidence from preclinical models and genetic evidence from humans suggest that members of the MS4A family have key roles in different pathological settings, including cancer, infectious diseases, and neurodegeneration. Therefore, MS4A family members might serve as candidate biomarkers and therapeutic targets for various conditions.


Assuntos
Doença , Homeostase , Imunidade , Tetraspaninas/fisiologia , Antígenos CD20 , Linfócitos B , Humanos , Macrófagos , Proteínas de Membrana
12.
Nutrients ; 13(8)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34444809

RESUMO

Alcohol use has been causally linked to more than 200 disease and injury conditions, as defined by three-digit ICD-10 codes. The understanding of how alcohol use is related to these conditions is essential to public health and policy research. Accordingly, this study presents a narrative review of different dose-response relationships for alcohol use. Relative-risk (RR) functions were obtained from various comparative risk assessments. Two main dimensions of alcohol consumption are used to assess disease and injury risk: (1) volume of consumption, and (2) patterns of drinking, operationalized via frequency of heavy drinking occasions. Lifetime abstention was used as the reference group. Most dose-response relationships between alcohol and outcomes are monotonic, but for diabetes type 2 and ischemic diseases, there are indications of a curvilinear relationship, where light to moderate drinking is associated with lower risk compared with not drinking (i.e., RR < 1). In general, women experience a greater increase in RR per gram of alcohol consumed than men. The RR per gram of alcohol consumed was lower for people of older ages. RRs indicated that alcohol use may interact synergistically with other risk factors, in particular with socioeconomic status and other behavioural risk factors, such as smoking, obesity, or physical inactivity. The literature on the impact of genetic constitution on dose-response curves is underdeveloped, but certain genetic variants are linked to an increased RR per gram of alcohol consumed for some diseases. When developing alcohol policy measures, including low-risk drinking guidelines, dose-response relationships must be taken into consideration.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Doença , Mortalidade , Fatores Etários , Causalidade , Relação Dose-Resposta a Droga , Humanos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fumar
13.
Life Sci ; 284: 119908, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34453943

RESUMO

Genetic disorders and congenital abnormalities are present in 2-5% of births all over the world and can cause up to 50% of all early childhood deaths. The establishment of sophisticated and controlled techniques for customizing DNA manipulation is significant for the therapeutic role in such disorders and further research on them. One such technique is CRISPR that is significant towards optimizing genome editing and therapies, metabolic fluxes as well as artificial genetic systems. CRISPR-Cas9 is a molecular appliance that is applied in the areas of genetic and protein engineering. The CRISPR-CAS system is an integral element of prokaryotic adaptive immunity that allows prokaryotic cells to identify and kill any foreign DNA. The Gene editing property of CRISPR finds various applications like diagnostics and therapeutics in cancer, neurodegenerative disorders, genetic diseases, blindness, etc. This review discusses applications of CRISPR as a therapeutic in various disorders including several genetic diseases (including sickle cell anemia, blindness, thalassemia, cystic fibrosis, hereditary tyrosinemia type I, duchenne muscular dystrophy, mitochondrial disorders), Cancer, Huntington's disease and viral infections (like HIV, COVID, etc.) along with the prospects concerning them. CRISPR-based therapy is also being researched and defined for COVID-19. The related mechanism of CRISPR has been discussed alongside highlighting challenges involved in therapeutic applications of CRISPR.


Assuntos
Sistemas CRISPR-Cas/genética , Animais , COVID-19/terapia , COVID-19/virologia , Ensaios Clínicos como Assunto , Doença/genética , Edição de Genes , Humanos , SARS-CoV-2/fisiologia
14.
Life Sci ; 284: 119914, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34453949

RESUMO

Macrophages, an important part of human immune system, possess a high plasticity and heterogeneity (macrophage polarization) as classically activated macrophages (M1) and alternatively activated macrophages (M2), which exert pro-inflammatory/anti-tumor and anti-inflammatory/pro-tumor effects, respectively. Thus, drug development in induction of macrophage polarization could be used to treat different human diseases. This review summarizes the recent advancement on modulation of macrophage polarization and its related molecular mechanisms induced by a number of agents. Research on the anti-inflammatory drugs to regulate the macrophage polarization accounts for a large proportion in the field and types of diseases investigated could include atherosclerosis, enteritis, nephritis, and the nervous system and skeletal diseases, while study of the anti-tumor agents to modify macrophage polarization is a novel area of research. Future study of the molecular mechanisms by which the different agents regulate the macrophage polarization could lead to an effective control of various human diseases, including inflammation and cancers.


Assuntos
Polaridade Celular , Doença , Macrófagos/citologia , Preparações Farmacêuticas/metabolismo , Animais , Polaridade Celular/genética , Humanos , Macrófagos/metabolismo , Transdução de Sinais/genética
15.
Am J Hum Genet ; 108(8): 1502-1511, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34256028

RESUMO

Predicting the effect of a mutated gene before the onset of symptoms of genetic diseases would greatly facilitate diagnosis and potentiate early intervention. There have been myriad attempts to predict the effects of single-nucleotide variants. However, the applicability of these efforts does not scale to co-occurring variants. Furthermore, an increasing number of protein therapeutics contain co-occurring nucleotide variations, adding uncertainty during development to the safety and efficiency of these drugs. Co-occurring nucleotide variants may often have synergistic, additive, or antagonistic effects on protein attributes, further complicating the task of outcome prediction. We tested four models based on the cooperative and antagonistic effects of co-occurring variants to predict pathogenicity and effectiveness of protein therapeutics. A total of 30 attributes, including amino acid and nucleotide features, as well as existing single-variant effect prediction tools, were considered on the basis of previous studies on single-nucleotide variants. Importantly, the effects of synonymous variants, often seen in protein therapeutics, were also included in our models. We used 12 datasets of people with monogenic diseases and controls with co-occurring genetic variants to evaluate the accuracy of our models, accomplishing a degree of accuracy comparable to that of prediction tools for single-nucleotide variants. More importantly, our framework is generalizable to new, well-curated datasets of monogenic diseases and new variant scoring tools. This approach successfully assists in addressing the challenging task of predicting the effect of co-occurring variants on pathogenicity and protein effectiveness and is applicable for a wide range of protein therapeutics and genetic diseases.


Assuntos
Biologia Computacional/métodos , Doença/genética , Genoma Humano , Mutação , Polimorfismo de Nucleotídeo Único , Proteoma/análise , Humanos , Proteoma/metabolismo
16.
Nutrients ; 13(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200819

RESUMO

Curcumin is one of the most frequently researched herbal substances; however, it has been reported to have a poor bioavailability and fast metabolism, which has led to doubts about its effectiveness. Curcumin has antioxidant and anti-inflammatory effects, and has demonstrated favorable health effects. Nevertheless, well-reported in vivo pharmacological activities of curcumin are limited by its poor solubility, bioavailability, and pharmacokinetic profile. The bidirectional interactions between curcumin and gut microbiota play key roles in understanding the ambiguity between the bioavailability and biological activity of curcumin, including its wider health impact.


Assuntos
Curcumina/farmacologia , Microbiota/efeitos dos fármacos , Animais , Disponibilidade Biológica , Curcumina/metabolismo , Doença , Exercício Físico/fisiologia , Saúde , Humanos
17.
Nutrients ; 13(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201670

RESUMO

Demonstrating in an unambiguous manner that a diet, let alone a single product, 'optimizes' health, presents an enormous challenge. The least complicated is when the starting situation is clearly suboptimal, like with nutritional deficiencies, malnutrition, unfavourable lifestyle, or due to disease or ageing. Here, desired improvements and intervention strategies may to some extent be clear. However, even then situations require approaches that take into account interactions between nutrients and other factors, complex dose-effect relationships etc. More challenging is to substantiate that a diet or a specific product optimizes health in the general population, which comes down to achieve perceived, 'non-medical' or future health benefits in predominantly healthy persons. Presumed underlying mechanisms involve effects of non-nutritional components with subtle and slowly occurring physiological effects that may be difficult to translate into measurable outcomes. Most promising strategies combine classical physiological concepts with those of 'multi-omics' and systems biology. Resilience-the ability to maintain or regain homeostasis in response to stressors-is often used as proxy for a particular health domain. Next to this, quantifying health requires personalized strategies, measurements preferably carried out remotely, real-time and in a normal living environment, and experimental designs other than randomized controlled trials (RCTs), for example N-of-1 trials.


Assuntos
Saúde , Fenômenos Fisiológicos da Nutrição , Biomarcadores/metabolismo , Doença , Objetivos , Humanos , Fatores de Risco
18.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200507

RESUMO

Long noncoding RNAs exceeding a length of 200 nucleotides play an important role in ensuring cell functions and proper organism development by interacting with cellular compounds such as miRNA, mRNA, DNA and proteins. However, there is an additional level of lncRNA regulation, called lncRNA epigenetics, in gene expression control. In this review, we describe the most common modified nucleosides found in lncRNA, 6-methyladenosine, 5-methylcytidine, pseudouridine and inosine. The biosynthetic pathways of these nucleosides modified by the writer, eraser and reader enzymes are important to understanding these processes. The characteristics of the individual methylases, pseudouridine synthases and adenine-inosine editing enzymes and the methods of lncRNA epigenetics for the detection of modified nucleosides, as well as the advantages and disadvantages of these methods, are discussed in detail. The final sections are devoted to the role of modifications in the most abundant lncRNAs and their functions in pathogenic processes.


Assuntos
Doença/etiologia , Epigênese Genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Humanos
19.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201121

RESUMO

Eva-1 homolog A (EVA1A) is regarded as TMEM166 (transmembrane protein 166) or FAM176A (family with sequence similarity 176) and a lysosome and endoplasmic reticulum-associated protein involved in regulating autophagy and apoptosis. EVA1A regulates embryonic neurogenesis, cardiac remodeling, islet alpha-cell functions, acute liver failure, and hepatitis B virus replication. However, the related mechanisms are not fully clear. Autophagy is a process in which cells transfer pathogens, abnormal proteins and organelles to lysosomes for degradation. It plays an important role in various physiological and pathological processes, including cancer, aging, neurodegeneration, infection, heart disease, development, cell differentiation and nutritional starvation. Recently, there are many studies on the important role of EVA1A in many physiological and pathological processes by regulating autophagy. However, the related molecular mechanisms need further study. Therefore, we summarize the above-mentioned researches about the role of EVA1A in physiological and pathological processes through regulating autophagy in order to provide theoretical basis for future researches.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Doença/etiologia , Homeostase , Proteínas de Membrana/metabolismo , Animais , Humanos
20.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203830

RESUMO

Insulin is a polypeptide hormone mainly secreted by ß cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.


Assuntos
Doença , Saúde , Insulina/metabolismo , Animais , Humanos , Secreção de Insulina , Fígado/metabolismo , Transdução de Sinais
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