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1.
Clin Genet ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38774940

RESUMO

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

2.
Clin Genet ; 103(3): 341-345, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36273379

RESUMO

Isolated syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover a novel heterozygous missense variant c.2915G > C: p.Arg972Pro in AFF3 on chromosome 2q11.2 in a family with isolated syndactyly in hands and feet. AFF3 belongs to a family of nuclear transcription activating factors and is involved in limb dorsoventral patterning. The variant Arg972Pro is located near the C terminus, a region that is yet to be associated with human disorders. Functional studies did not show a difference in the stability or subcellular localization of the mutant and wild type proteins. Instead, overexpression in zebrafish embryos suggests that Arg972Pro is a loss-of-function allele. These results suggest that variants in the C terminus of AFF3 may cause a phenotype distinct from previously characterized AFF3 variants.


Assuntos
Deformidades Congênitas dos Membros , Sindactilia , Animais , Humanos , Peixe-Zebra/genética , Sindactilia/genética , Deformidades Congênitas dos Membros/genética , Fatores de Transcrição/genética , Mutação de Sentido Incorreto , Linhagem , Proteínas Nucleares/genética
3.
Cell Mol Neurobiol ; 43(8): 4071-4101, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37955798

RESUMO

MECP2 and its product methyl-CpG binding protein 2 (MeCP2) are associated with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), which are inflammatory, autoimmune, and demyelinating disorders of the central nervous system (CNS). However, the mechanisms and pathways regulated by MeCP2 in immune activation in favor of MS and NMOSD are not fully understood. We summarize findings that use the binding properties of MeCP2 to identify its targets, particularly the genes recognized by MeCP2 and associated with several neurological disorders. MeCP2 regulates gene expression in neurons, immune cells and during development by modulating various mechanisms and pathways. Dysregulation of the MeCP2 signaling pathway has been associated with several disorders, including neurological and autoimmune diseases. A thorough understanding of the molecular mechanisms underlying MeCP2 function can provide new therapeutic strategies for these conditions. The nervous system is the primary system affected in MeCP2-associated disorders, and other systems may also contribute to MeCP2 action through its target genes. MeCP2 signaling pathways provide promise as potential therapeutic targets in progressive MS and NMOSD. MeCP2 not only increases susceptibility and induces anti-inflammatory responses in immune sites but also leads to a chronic increase in pro-inflammatory cytokines gene expression (IFN-γ, TNF-α, and IL-1ß) and downregulates the genes involved in immune regulation (IL-10, FoxP3, and CX3CR1). MeCP2 may modulate similar mechanisms in different pathologies and suggest that treatments for MS and NMOSD disorders may be effective in treating related disorders. MeCP2 regulates gene expression in MS and NMOSD. However, dysregulation of the MeCP2 signaling pathway is implicated in these disorders. MeCP2 plays a role as a therapeutic target for MS and NMOSD and provides pathways and mechanisms that are modulated by MeCP2 in the regulation of gene expression.


Assuntos
Doenças Autoimunes , Esclerose Múltipla , Neuromielite Óptica , Humanos , Esclerose Múltipla/complicações , Neuromielite Óptica/genética , Neuromielite Óptica/tratamento farmacológico , Proteína 2 de Ligação a Metil-CpG/genética , Doenças Autoimunes/complicações , Citocinas
4.
Chem Rec ; 23(2): e202200149, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36408911

RESUMO

Recently, the growing demand for a renewable and sustainable fuel alternative is contingent on fuel cell technologies. Even though it is regarded as an environmentally sustainable method of generating fuel for immediate concerns, it must be enhanced to make it extraordinarily affordable, and environmentally sustainable. Hydrogen (H2 ) synthesis by electrochemical water splitting (ECWS) is considered one of the foremost potential prospective methods for renewable energy output and H2 society implementation. Existing massive H2 output is mostly reliant on the steaming reformation of carbon fuels that yield CO2 together with H2 and is a finite resource. ECWS is a viable, efficient, and contamination-free method for H2 evolution. Consequently, developing reliable and cost-effective technology for ECWS was a top priority for scientists around the globe. Utilizing renewable technologies to decrease total fuel utilization is crucial for H2 evolution. Capturing and transforming the fuel from the ambient through various renewable solutions for water splitting (WS) could effectively reduce the need for additional electricity. ECWS is among the foremost potential prospective methods for renewable energy output and the achievement of a H2 -based economy. For the overall water splitting (OWS), several transition-metal-based polyfunctional metal catalysts for both cathode and anode have been synthesized. Furthermore, the essential to the widespread adoption of such technology is the development of reduced-price, super functional electrocatalysts to substitute those, depending on metals. Many metal-premised electrocatalysts for both the anode and cathode have been designed for the WS process. The attributes of H2 and oxygen (O2 ) dynamics interactions on the electrodes of water electrolysis cells and the fundamental techniques for evaluating the achievement of electrocatalysts are outlined in this paper. Special emphasis is paid to their fabrication, electrocatalytic performance, durability, and measures for enhancing their efficiency. In addition, prospective ideas on metal-based WS electrocatalysts based on existing problems are presented. It is anticipated that this review will offer a straight direction toward the engineering and construction of novel polyfunctional electrocatalysts encompassing superior efficiency in a suitable WS technique.

5.
Chem Rec ; 23(5): e202200171, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37066717

RESUMO

Graphitic carbon nitride (g-C3 N4 ) has gained tremendous interest in the sector of power transformation and retention, because of its distinctive stacked composition, adjustable electronic structure, metal-free feature, superior thermodynamic durability, and simple availability. Furthermore, the restricted illumination and extensive recombination of photoexcitation electrons have inhibited the photocatalytic performance of pure g-C3 N4 . The dimensions of g-C3 N4 may impact the field of electronics confinement; as a consequence, g-C3 N4 with varying dimensions shows unique features, making it appropriate for a number of fascinating uses. Even if there are several evaluations emphasizing on the fabrication methods and deployments of g-C3 N4 , there is certainly an insufficiency of a full overview, that exhaustively depicts the synthesis and composition of diverse aspects of g-C3 N4 . Consequently, from the standpoint of numerical simulations and experimentation, several legitimate methodologies were employed to deliberately develop the photocatalyst and improve the optimal result, including elements loading, defects designing, morphological adjustment, and semiconductors interfacing. Herein, this evaluation initially discusses different dimensions, the physicochemical features, modifications and interfaces design development of g-C3 N4 . Emphasis is given to the practical design and development of g-C3 N4 for the various power transformation and inventory applications, such as photocatalytic H2 evolution, photoreduction of CO2 source, electrocatalytic H2 evolution, O2 evolution, O2 reduction, alkali-metal battery cells, lithium-ion batteries, lithium-sulfur batteries, and metal-air batteries. Ultimately, the current challenges and potential of g-C3 N4 for fuel transformation and retention activities are explored.

6.
Cell Mol Life Sci ; 79(2): 128, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35133502

RESUMO

The evolutionary necessity of aminoacyl-tRNA synthetases being associated into complex is unknown. Human lysyl-tRNA synthetase (LysRS) is one component of the multi-tRNA synthetase complex (MSC), which is not only critical for protein translation but also involved in multiple cellular pathways such as immune response, cell migration, etc. Here, combined with crystallography, CRISPR/Cas9-based genome editing, biochemistry, and cell biology analyses, we show that the structures of LysRSs from metazoan are more dynamic than those from single-celled organisms. Without the presence of MSC scaffold proteins, such as aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2), human LysRS is free from the MSC. The interaction with AIMP2 stabilizes the closed conformation of LysRS, thereby protects the essential aminoacylation activity under stressed conditions. Deleting AIMP2 from the human embryonic kidney 293 cells leads to retardation in cell growth in nutrient deficient mediums. Together, these results suggest that the evolutionary emergence of the MSC in metazoan might be to protect the aminoacyl-tRNA synthetase components from being modified or recruited for use in other cellular pathways.


Assuntos
Lisina-tRNA Ligase/metabolismo , Proteínas Nucleares/metabolismo , Aminoacilação , Células HEK293 , Humanos , Ligação Proteica , Biossíntese de Proteínas
7.
J Hum Genet ; 67(5): 253-259, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34857885

RESUMO

Cenani-Lenz syndrome (CLS) is a rare autosomal-recessive congenital disorder affecting development of distal limbs. It is characterized mainly by syndactyly and/or oligodactyly, renal anomalies, and characteristic facial features. Mutations in the LRP4 gene, located on human chromosome 11p11.2-q13.1, causes the CLS. The gene LRP4 encodes a low-density lipoprotein receptor-related protein-4, which mediates SOST-dependent inhibition of bone formation and Wnt signaling. In the study, presented here, three families of Pakistani origin, segregating CLS in the autosomal recessive manner were clinically and genetically characterized. In two families (A and B), microsatellite-based homozygosity mapping followed by Sanger sequencing identified a novel homozygous missense variant [NM_002334.3: c.295G>C; p.(Asp99His)] in the LRP4 gene. In the third family C, exome sequencing revealed a second novel homozygous missense variant [NM_002334.3: c.1633C>T; p.(Arg545Trp)] in the same gene. To determine the functional relevance of these variants, we tested their ability to inhibit canonical WNT signaling in a luciferase assay. Wild type LRP4 was able to inhibit LRP6-dependent WNT signaling robustly. The two mutants p.(Asp99His) and p.(Arg545Trp) inhibited WNT signaling less effectively, suggesting they reduced LRP4 function.


Assuntos
Proteínas Relacionadas a Receptor de LDL , Sindactilia , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Masculino , Linhagem , Sindactilia/genética , Via de Sinalização Wnt/genética
8.
BMC Infect Dis ; 21(1): 426, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957883

RESUMO

OBJECTIVE: Rotavirus A (RVA) is a significant cause of severe diarrheal illness and one of the common causes of death in children under the age of five. This study was aimed at detecting the prevalence of RVA in Pakistan after rotavirus vaccines were introduced. Fecal samples were obtained from 813 children from different hospitals in Rawalpindi and Islamabad, Pakistan, from January 2018 to December 2018. To obtain additional information from the parents / guardians of the children, a standard questionnaire was used. RESULTS: Using an enzyme-linked immunosorbent assay kit (ELISA), rotavirus antigen was detected and ELISA positive samples were subjected to reverse transcription PCR (RT-PCR). The findings showed 22% prevalence of RVA in children with acute gastroenteritis (AGE) via ELISA and 21% prevalence via RT-PCR in children with AGE. There was no statistically significant difference between gender, age and RVA infections. The winter, spring and fall/autumn seasons were statistically significant for RVA prevalence. CONCLUSION: The present study will provide post vaccine prevalence data for the health policy makers. The implementation of rotavirus vaccines, along with adequate nutrition for babies, clean water supply and maternal hygienic activities during infant feeding, is recommended. Furthermore, continuous surveillance is mandatory in the whole country to calculate the disease burden caused by RVA.


Assuntos
Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Criança , Pré-Escolar , Diarreia/epidemiologia , Diarreia/virologia , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Feminino , Gastroenterite/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Paquistão/epidemiologia , Prevalência , Rotavirus/isolamento & purificação , Infecções por Rotavirus/virologia , Estações do Ano
9.
Microb Pathog ; 114: 116-123, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29174698

RESUMO

This study describes the first ever utilization of cell free aqueous extract of cyanobacterium Leptolyngbya JSC-1 as a source of strong reducing and stabilizing agents for the optimal biofabrication of gold nanoparticles (AuNPs) through an eco-friendly synthetic route. Well dispersed crystalline AuNPs of spherical morphology with a particle size of 100-200 nm were prepared. FTIR spectral analysis was then performed to characterize the possible functionalities of JSC-1 extract, mainly involved in stabilizing and formation of AuNPs. Based on the redox potential of JSC-1 extract, it was further confirmed that the extract provide a strong reducing environment in the reaction medium and causes reduction of gold ions. The resultant AuNPs were then explored to find out their photo-catalytic activity for methylene blue and antibacterial activities against E. coli (18 ± 2 mm) and S. aureus (14 ± 2 mm). It has been mechanistically identified that AuNPs caused bacterial membrane damage and cell disruption by inducing the production of intracellular reactive oxygen species (ROS). Together, these finding reveals that biochemically capped AuNPs are the promising antibacterial agents that induce oxidative stress in the two bacterial species evaluated and cause their membrane disruption leading to cell leakage and death.


Assuntos
Antibacterianos/farmacologia , Cianobactérias/metabolismo , Excipientes/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Antibacterianos/química , Bactérias/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Excipientes/química , Ouro/farmacologia , Química Verde , Testes de Sensibilidade Microbiana , Nanotecnologia/métodos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos
10.
BMC Med ; 13: 156, 2015 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-26137966

RESUMO

BACKGROUND: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients. METHODS: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model. RESULTS: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45). CONCLUSIONS: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.


Assuntos
Anexina A1/genética , Adulto , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Genes BRCA1/fisiologia , Genes BRCA2/fisiologia , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Prognóstico
11.
BMC Cancer ; 14: 908, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25472026

RESUMO

BACKGROUND: PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performance with the Predict model that includes HER2 status (v2). METHODS: The validation study was based on 1,726 patients with EBC treated in Nottingham between 1989 and 1998. KI67 positivity for PREDICT is defined as >10% of tumour cells staining positive. ROC curves were constructed for Predict models with (v3) and without (v2) KI67 input. Comparison was made using the method of DeLong. RESULTS: In 1274 ER+ patients the predicted number of events at 10 years increased from 196 for v2 to 204 for v3 compared to 221 observed. The area under the ROC curve (AUC) improved from 0.7611 to 0.7676 (p=0.005) in ER+ patients and from 0.7546 to 0.7595 (p=0.0008) in all 1726 patients (ER+ and ER-). CONCLUSION: Addition of KI67 to PREDICT has led to a statistically significant improvement in the model performance for ER+ patients and will aid clinical decision making in these patients. Further studies should determine whether other markers including gene expression profiling provide additional prognostic information to that provided by PREDICT.


Assuntos
Neoplasias da Mama/química , Neoplasias da Mama/patologia , Antígeno Ki-67/análise , Modelos Teóricos , Receptor ErbB-2/análise , Adulto , Área Sob a Curva , Neoplasias da Mama/mortalidade , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Receptores de Estrogênio/análise , Carga Tumoral
12.
Sci Rep ; 14(1): 9627, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671024

RESUMO

In this study, an accurate analytical solution is presented for fuzzy FPDEs. It is done by using a novel method called the Laplace-residual power series (LRPSM) to build a series solution to the given problems. The fundamental instruments of the employed method are the Laplace transform, fractional Laurent, and fractional power series. Using the idea of a limit at infinity, we provide a series solution to a fuzzy FPDE with quick convergence and simple coefficient finding. We analyze three cases to obtain approximate and exact solutions to show the effectiveness and reliability of the Laplace- residual power series approach. To demonstrate the accuracy of the suggested procedure, we compare the findings to the real data.

13.
Front Pharmacol ; 15: 1332184, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595924

RESUMO

Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine (4). The novel conjugates 6 (a-o) were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound 4 was refluxed with various aldehydes and ketones 5 (a-o) for 5-8 h in methanol at 60°C-90°C. This research modified the drug in a step-by-step manner to develop therapeutic properties as a tyrosinase inhibitor. The structures of synthesized ligands 6 (a-o) were established based on spectral and analytical data. The synthesized compounds 6 (a-o) were screened against tyrosinase enzyme. Kojic acid was taken as standard. All the prepared compounds 6 (a-o) have good inhibition potential against the enzyme tyrosinase. Compounds 6o, 6b, 6f, and 6k depicted excellent antityrosinase activity. Compound 6k, with an IC50 value of 5.34 ± 0.58 µM, is as potent as the standard kojic acid (IC50 6.04 ± 0.11 µM), standing out among all synthesized compounds 6 (a-o). The in silico studies of the conjugates 6 (a-o) were evaluated via PatchDock. Compound 6k showed a binding affinity score of 8,999 and an atomic contact energy (ACE) value of -219.66 kcal/mol. The structure-activity relationship illustrated that the presence of dihydropyridine nuclei and some activating groups at the ortho and para positions of the benzylideneimine moiety is the main factor for good tyrosinase activity. The compound 6k could be used as a lead compound for drug modification as a tyrosinase inhibitor for skin care, anticancer medication, and antibrowning for fruits and vegetables.

14.
Environ Pollut ; 346: 123597, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38369096

RESUMO

Coconut shell activated carbon (CNSAC) was applied as a filter layer in hybrid vertical subsurface flow constructed wetland (H-VSSF-CW), in order to enhance the multi-metal removal efficiency of the constructed wetland (CW) and to reduce heavy metal accumulation on Salvinia cucullata. Treatment P + AC, (having CNSAC filter layer), showed 32, 21 and 34% more Cd, Cr, and Pb removal efficiency than treatment P (without CNSAC layer). CNSAC activated carbon adsorbed Cd and Pb and Cr by functional groups -NH, -NO2, -C-O, -OH and -CO, and significantly reduced Cd and Pb exposure to S. cucullate. Chromium adsorption by CNSAC filter layer was half (just 25% of total input) of the Cd and Pb. In treatment P, due to high Cd, Pb and Cr accumulation in S. cucullate, the antioxidant defense mechanism of the plant was collapsed and cell death was observed, which in turn has resulted reduced biomass gain (5% reduction). On the other hand, in treatment P + AC, an antioxidant defense mechanism was active in the form significantly (p ≤ 0.05) increased of SOD, CAT and proline content while reduced MDA, EL, %EB and soluble sugar. So, the application of CNSAC increased the heavy metal removal efficiency of H-VSSF-CW by adsorption of a considerable share of heavy metal and hence, reduced the heavy metal load/exposure to S. cucullate.


Assuntos
Metais Pesados , Traqueófitas , Cádmio/análise , Áreas Alagadas , Cocos/metabolismo , Antioxidantes , Carvão Vegetal , Biodegradação Ambiental , Chumbo , Eliminação de Resíduos Líquidos/métodos , Metais Pesados/análise
15.
Curr Probl Cardiol ; 49(2): 102202, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37967800

RESUMO

Implementing Single-cell RNA sequencing (scRNA-seq) has significantly enhanced our comprehension of cardiovascular diseases (CVDs), providing new opportunities to strengthen the prevention of CVDs progression. Cardiovascular diseases continue to be the primary cause of death worldwide. Improving treatment strategies and patient risk assessment requires a deeper understanding of the fundamental mechanisms underlying these disorders. The advanced and widespread use of Single-cell RNA sequencing enables a comprehensive investigation of the complex cellular makeup of the heart, surpassing essential descriptive aspects. This enhances our understanding of disease causes and directs functional research. The significant advancement in understanding cellular phenotypes has enhanced the study of fundamental cardiovascular science. scRNA-seq enables the identification of discrete cellular subgroups, unveiling previously unknown cell types in the heart and vascular systems that may have relevance to different disease pathologies. Moreover, scRNA-seq has revealed significant heterogeneity in phenotypes among distinct cell subtypes. Finally, we will examine current and upcoming scRNA-seq studies about various aspects of the cardiovascular system, assessing their potential impact on our understanding of the cardiovascular system and offering insight into how these technologies may revolutionise the diagnosis and treatment of cardiac conditions.


Assuntos
Doenças Cardiovasculares , Cardiopatias , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , Análise da Expressão Gênica de Célula Única , Medição de Risco , Análise de Sequência de RNA
16.
Int Rev Immunol ; 43(4): 229-247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343353

RESUMO

BACKGROUND: The gut microbiome plays a role in the development and progression of colorectal cancer (CRC). AIM AND OBJECTIVE: This review focuses on whether the gut microbiome is involved in the development and regulation of the host immune system. METHODS: The gut microbiome can influence the production and activity of immune cells and molecules that help to maintain the integrity of the intestinal barrier and prevent inflammation. Gut microbiota modulates the anti-cancer immune response. The gut microbiota can influence the function of immune cells, like T cells, that recognize and eliminate cancer cells. Gut microbiota can affect various aspects of cancer progression and the efficacy of various anti-cancer treatments. RESULTS: Gut microbiota provide promise as a potential biomarker to identify the effect of immunotherapy and as a target for modulation to improve the efficacy of immunotherapy in CRC treatment. CONCLUSION: The potential synergistic effect between the gut microbiome and anti-cancer treatment modalities provides an interest in developing strategies to modulate the gut microbiome to improve the efficacy of anti-cancer treatment.


This review focuses on the gut microbiome in the development and regulation of the host immune system. Gut microbiota provides potential biomarkers to identify the effect of immunotherapy and as a target for modulation of immunotherapy in the treatment of CRC. This provides potential synergistic effects between the gut microbiome and anti-cancer treatment modalities.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal/imunologia , Animais , Imunoterapia/métodos , Probióticos/uso terapêutico
17.
Heliyon ; 10(6): e26838, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515670

RESUMO

Background: Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique. Constant electric current is passed through the patient's scalp with the aim of modulating cortical excitability. Stroke is a cerebrovascular disease characterized by hemorrhage or cerebral ischemia. This systematic review and meta-analysis are aimed at comparing the efficacy of motor cortex stimulation with that of cerebellar stimulation by using transcranial direct current stimulation. Method: Google Scholar, PubMed, EMBASE, Cochrane CENTRAL, and Physiotherapy Evidence Database (Pedro) databases were searched for studies. The extracted qualitative data was synthesized systematically. Cochrane RevMan software was used to conduct a meta-analysis of quantitative data. The fixed effects mean difference of the collected data was calculated at a 95% confidence interval (CI) for the changes in balance and side effects. Results: This research included 10 articles with seven studies assessing changes in balance (outcome measured in CoP and FMA scores) and side effects (tingling and itching were the most prevalent). There was no significant difference between the efficacy levels of m1-tDCS versus ctDCS (P = 0.18), m1-tDCS versus sham (P = 0.92), and ctDCS versus sham (P = 0.19). Itching and tingling sensation were the most common and were significantly prevalent in sham interventions (P < 0.00001). Conclusion: We found that motor cortex and cerebellar stimulations are both effective in improving motor function in stroke patients. There are no adverse effects to using the interventions besides mild itching and tingling experienced during the stimulation.

18.
Curr Probl Cardiol ; 49(2): 102222, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38000567

RESUMO

Patients with preexisting cardiovascular disease or those at high risk for developing the condition are often offered exercise as a form of therapy. Patients with cancer who are at an increased risk for cardiovascular issues are increasingly encouraged to participate in exercise-based, interdisciplinary programs due to the positive correlation between these interventions and clinical outcomes following myocardial infarction. Diabetic cardiomyopathy (DC) is a cardiac disorder that arises due to disruptions in the homeostasis of individuals with diabetes. One of the primary reasons for mortality in individuals with diabetes is the presence of cardiac structural damage and functional abnormalities, which are the primary pathological features of DC. The aetiology of dilated cardiomyopathy is multifaceted and encompasses a range of processes, including metabolic abnormalities, impaired mitochondrial function, dysregulation of calcium ion homeostasis, excessive cardiomyocyte death, and fibrosis. In recent years, many empirical investigations have demonstrated that exercise training substantially impacts the prevention and management of diabetes. Exercise has been found to positively impact the recovery of diabetes and improve several metabolic problem characteristics associated with DC. One potential benefit of exercise is its ability to increase systolic activity, which can enhance cardiometabolic and facilitate the repair of structural damage to the heart caused by DC, leading to a direct improvement in cardiac health. In contrast, exercise has the potential to indirectly mitigate the pathological progression of DC through its ability to decrease circulating levels of sugar and fat while concurrently enhancing insulin sensitivity. A more comprehensive understanding of the molecular mechanism via exercise facilitates the restoration of DC disease must be understood. Our goal in this review was to provide helpful information and clues for developing new therapeutic techniques for motion alleviation DC by examining the molecular mechanisms involved.


Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , Infarto do Miocárdio , Humanos , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Exercício Físico
19.
Curr Probl Cardiol ; 49(3): 102397, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232921

RESUMO

Cardiovascular diseases (CVDs) are still leading to a significant number of deaths worldwide despite the remarkable advancements in medical technology and pharmacology. Managing patients with established CVDs is a challenge for healthcare providers as it requires reducing the chances of recurring cardiovascular events. On the other hand, changing one's way of life can also significantly impact this area, reducing the likelihood of cardiovascular disease and death through their unique advantages. Consequently, it is advisable for healthcare providers to regularly advise their patients with coronary issues to participate in organized physical exercise and improve their overall physical activity. Additionally, patients should adhere to a diet that promotes heart health, cease smoking, avoid exposure to secondhand smoke, and address any psychosocial stressors that may heighten the risk of cardiovascular problems. These lifestyle therapies, whether used alongside drug therapy or on their own in patients who may have difficulty tolerating medications, face financial barriers, or experience ineffectiveness, can substantially reduce cardiovascular mortality and the likelihood of recurring cardiac events. Despite the considerable advancements in creating interventions, it is still necessary to determine the optimal intensity, duration, and delivery method for these interventions. Furthermore, it is crucial to carry out further investigations incorporating extended monitoring and assessment of clinical outcomes to get a more comprehensive comprehension of the efficacy of these therapies. Presenting the findings within the framework of "lifestyle medicine," this review seeks to offer a thorough synopsis of the most recent scientific investigations into the potential of behavioral modifications to lower cardiovascular disease risk.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estilo de Vida , Exercício Físico , Dieta
20.
Curr Probl Cardiol ; 49(3): 102390, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232927

RESUMO

Long non-coding RNAs (lncRNAs) are RNA molecules that regulate gene expression at several levels, including transcriptional, post-transcriptional, and translational. They have a length of more than 200 nucleotides and cannot code. Many human diseases have been linked to aberrant lncRNA expression, highlighting the need for a better knowledge of disease etiology to drive improvements in diagnostic, prognostic, and therapeutic methods. Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. LncRNAs play an essential role in the complex process of heart formation, and their abnormalities have been associated with several CVDs. This Review article looks at the roles and relationships of long non-coding RNAs (lncRNAs) in a wide range of CVDs, such as heart failure, myocardial infarction, atherosclerosis, and cardiac hypertrophy. In addition, the review delves into the possible uses of lncRNAs in diagnostics, prognosis, and clinical treatments of cardiovascular diseases. Additionally, it considers the field's future prospects while examining how lncRNAs might be altered and its clinical applications.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Infarto do Miocárdio , RNA Longo não Codificante , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Prognóstico
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