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1.
Prog Mol Biol Transl Sci ; 204: 1-43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38458734

RESUMO

Atherosclerosis represents a pathological state that affects the arterial system of the organism. This chronic, progressive condition is typified by the accumulation of atheroma within arterial walls. Modulation of RNA molecules through RNA-based therapies has expanded the range of therapeutic options available for neurodegenerative diseases, infectious diseases, cancer, and, more recently, cardiovascular disease (CVD). Presently, microRNAs and small interfering RNAs (siRNAs) are the most widely employed therapeutic strategies for targeting RNA molecules, and for regulating gene expression and protein production. Nevertheless, for these agents to be developed into effective medications, various obstacles must be overcome, including inadequate binding affinity, instability, challenges of delivering to the tissues, immunogenicity, and off-target toxicity. In this comprehensive review, we discuss in detail the current state of RNA interference (RNAi)-based therapies.


Assuntos
Aterosclerose , MicroRNAs , Neoplasias , Humanos , Interferência de RNA , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Interferente Pequeno/uso terapêutico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Neoplasias/terapia , Aterosclerose/terapia , Aterosclerose/tratamento farmacológico
2.
Curr HIV Res ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38279732

RESUMO

OBJECTIVE: This article aimed to analyze upper endoscopic findings in the HIV patient population to elucidate the upper-gastrointestinal complications related to HIV infection. Gastrointestinal (GI) disorders in individuals living with HIV/AIDS exhibit diverse and often nonspecific manifestations, imposing substantial morbidity and mortality burdens. Endoscopic evaluation with biopsies is essential in the diagnosis and management of these conditions. Delayed treatment due to undetected GI abnormalities during endoscopic examinations can lead to poorer health outcomes. METHODS: This systematic review has determined the findings of upper-GI endoscopy of HIV-infected patients. Online databases of PubMed, Web of Science, Jisc Library Hub Discover, and Library of Congress have been searched using relevant keyword combinations. We have retrieved all the pertinent papers and reports published in English and screened them against inclusion/exclusion criteria for data extraction in two steps. First, titles/abstracts have been evaluated and then full-text screening has been performed by independent researchers. This study has adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. RESULTS: In this review, 24 articles have been included in the final analysis. The study has focused on the characteristics of participants and the findings of endoscopic evaluations. The participants of the study have been HIV-positive patients, and the majority of them have undergone endoscopy due to gastrointestinal symptoms. The biopsy regions primarily targeted have been observed to be the esophagus, stomach, and duodenum. The most common result of the biopsy specimens has been chronic active gastritis. CONCLUSION: To improve clinical practice, this systematic review sought to provide an up-to-date reference for upper gastrointestinal endoscopic findings of HIV-infected persons. Our results are in line with earlier research showing how effective endoscopy is for determining a precise diagnosis and directing care. The majority of HIV patients with gastrointestinal symptoms have been found to have opportunistic infections and persistent active gastritis as well as mucosal abnormalities of the upper gastrointestinal tract. Studies have shown that endoscopic and histological assessment can aid in the early detection and management of issues involving the upper gastrointestinal tract.

3.
Front Endocrinol (Lausanne) ; 14: 1230932, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881501

RESUMO

Introduction: Bone density regulation is considered one of the systems affected by thyroid hormones, leading to low bone density that can result in pathologic fractures, including hip fractures. This review aimed to update clinicians and researchers about the current data regarding the relationship between hip fractures and thyroid disorders. Methods: English papers were thoroughly searched in four main online databases of Scopus, Web of Science, PubMed, and Embase. Data extraction was done following two steps of screening/selection using distinct inclusion/exclusion criteria. This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and the Newcastle-Ottawa Scale (NOS) as bias assessment. Results: In total, 19 articles were included in the research. The risk of hip fractures in women with differentiated thyroid cancer (DTC) is higher than hip fractures caused by osteoporosis. Men with hyperthyroidism and subclinical hyperthyroidism are at higher risk for hip fracture. Also, a decrease in serum thyroid stimulating hormone (TSH) may be associated with an increased risk of hip fracture. Conclusion: Reaching a consensus conclusion regarding the association between subclinical thyroid dysfunction and hip fracture is not feasible due to the heterogenicity of evidence; however, there may be a higher risk of fracture in individuals with subclinical hyperthyroidism.


Assuntos
Fraturas do Quadril , Hipertireoidismo , Doenças da Glândula Tireoide , Masculino , Feminino , Humanos , Fraturas do Quadril/etiologia , Fraturas do Quadril/complicações , Doenças da Glândula Tireoide/complicações , Hipertireoidismo/complicações , Hormônios Tireóideos
4.
J Gene Med ; 25(9): e3521, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37132057

RESUMO

Monkeypox infection outbreaks have been observed sporadically in Africa, usually as a result of interaction with wildlife reservoirs. The genomes of the new strain range in size from 184.7 to 198.0 kb and are identified with 143-214 open reading frames. Viral cores are rapidly carried on microtubules away from the cell's perimeter and deeper into the cytoplasm once the virus and cell membranes fuse. Depending on the kind of exposure, patients with monkeypox may experience a febrile prodrome 5-13 days after exposure, which frequently includes lymphadenopathy, malaise, headaches, and muscle aches. A different diagnostic approach is available for monkeypox, including histopathological analysis, electron microscopy, immunoassays, polymerase chain reaction, genome sequencing, microarrays, loop-mediated isothermal amplification technology and CRISPR (i.e., "clustered regularly interspaced short palindromic repeats"). There are currently no particular, clinically effective treatments available for the monkeypox virus. An initial treatment is cidofovir. As a monophosphate nucleotide analog, cidofovir is transformed into an inhibitor of viral DNA polymerase by cellular kinases, which is analogous to cidofovir's function in inhibiting viral DNA synthesis. The European Medicine Agency and the Food and Drug Administration have both granted permission for IMVAMUNE, a replication-deficient, attenuated third-generation modified vaccinia Ankara vaccine, to be used for the prevention of smallpox and monkeypox in adults.


Assuntos
Mpox , Estados Unidos , Humanos , Mpox/diagnóstico , Mpox/tratamento farmacológico , Mpox/epidemiologia , Cidofovir/farmacologia , Cidofovir/uso terapêutico , Vaccinia virus/genética , Monkeypox virus/genética , Técnicas de Laboratório Clínico
5.
Drug Discov Today ; 28(3): 103470, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36572377

RESUMO

Familial hypercholesterolemia (FH) is a common autosomal codominant hereditary illness marked by the heightened risk of early atherosclerotic cardiovascular disease and high blood levels of low-density lipoprotein cholesterol (LDL-C). FH patients can have homozygous or heterozygous variants. This condition has been linked to variations in the genes for the LDL receptor (LDLR), apolipoprotein B, proprotein convertase subtilisin/Kexin 9 (PCSK9), and LDLR adaptor protein 1. Drugs such as statins, ezetimibe, and PCSK9 inhibitors are currently widely available, allowing for the theoretical normalization of plasma LDL-C levels mostly in patients with heterozygous FH. However, homozygous FH patients usually have a poor response to traditional lipid-lowering therapy and may have a poor prognosis at a young age. LDL apheresis and novel pharmacological therapies such as microsomal transfer protein inhibitors or anti-angiopoietin-like protein 3 monoclonal antibodies are extremely expensive and unavailable in most regions of the world. Therefore, the unmet need persists for these patients. In this review, we discuss the numerous gene delivery, gene editing, and stem cell manipulation techniques used in this study to correct FH-causing LDLR gene variations in vitro, ex vivo, and in vivo. Finally, we looked at a variety of studies that corrected genetic defects that caused FH using the ground-breaking clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology.


Assuntos
Hiperlipoproteinemia Tipo II , Pró-Proteína Convertase 9 , Humanos , LDL-Colesterol/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos
6.
AIDS Rev ; 25(4): 151-161, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38206792

RESUMO

Transporting and driving long distances might be associated with an increased risk of contracting HIV in truck drivers, which is recognized as a link to network transmission of HIV among this population. The present study aims to systematically review the prevalence and risk factors of HIV infection in truck drivers globally. A comprehensive search of the databases of Embase, PubMed, Scopus, and Web of Science was carried out. The original papers reporting statistics on the prevalence and risk factors of HIV infection among truck drivers were included. In this study, 23 original articles that met the eligibility criteria were reviewed. All articles were cross-sectional studies in which a total number of 16,315 truck drivers were studied to estimate the prevalence and risk factors of HIV infection. Findings indicated high HIV seroprevalence among truck drivers, with the highest prevalence of 56% in South Africa. HIV/AIDS awareness and condom use among truckers were reported low. Having sex with other men, circumcision status, time away from home, marital status, years working as a truck driver, education, income, and drug/alcohol use are the most important risk factors for HIV in truck drivers. Longer time on the road can increase the risk of infection by creating conditions for unsafe sex, in particular, having sex with other men. Low socioeconomic status exacerbates the condition. HIV risk-reduction interventions for long-distance truck drivers are necessary to enhance the awareness of sexually transmitted infections and introduce protective measures such as condoms.


Assuntos
Infecções por HIV , Masculino , Humanos , Infecções por HIV/epidemiologia , Prevalência , Estudos Soroepidemiológicos , Caminhoneiros , Veículos Automotores , Fatores de Risco , Comportamento Sexual
7.
Clin Case Rep ; 10(3): e05633, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35356190

RESUMO

Hypophosphatasia is a rare inherited disease defined by teeth and bone mineralization impairment leading to depletion of tissue non-specific alkaline phosphatase. We define a young woman diagnosed with hypophosphatasia (after several times alkaline phosphatase levels were low) was discovered following femoral fracture. A 30-year-old woman who presented for a history of early permanent teeth loss during the last 5 years and HPP-like symptoms in family history and bone radiograph verified bowing, deficient mineralization, and symmetrical subtrochanteric stress fractures of femurs was referred to our clinic for further management. Blood test findings defined raised phosphorus levels on two occasions at 6.2 and 5.7 mg/dl and insufficient 25-hydroxy vitamin D level. HPP early diagnosis and adequate treatment, depending on the clinical symptoms along with laboratory tests, could be effective in decreasing the suffering of the disease and side effects.

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