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1.
J Pharm Bioallied Sci ; 16(Suppl 1): S663-S665, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595469

RESUMO

Background: This study aims to explore the connection between obstructive sleep apnea (OSA) and temporomandibular joint disorders (TMD) through a case-control investigation. OSA is a sleep-related breathing disorder that affects breathing during sleep, whereas TMD involves pain and dysfunction in the jaw joint. Understanding any potential association between these two conditions could contribute to improved diagnostic and therapeutic approaches. Materials and Methods: A total of 50 participants were included in both the OSA group and the control group. Participants with diagnosed OSA constituted the OSA group, whereas individuals without OSA formed the control group. TMD symptoms were assessed using standardized diagnostic criteria. Statistical analysis was performed to compare the prevalence of TMD symptoms between the two groups. Results: In the OSA group, 36 out of 50 participants exhibited TMD symptoms, whereas in the control group, 18 out of 50 participants displayed such symptoms. The calculated P value was found to be 0.023, indicating a statistically significant association between OSA and TMD. Conclusion: The findings of this study suggest a notable association between OSA and TMD. Individuals with OSA are more likely to experience TMD symptoms compared to those without OSA. This underscores the importance of considering TMD symptoms in individuals with OSA and vice versa for a comprehensive approach to diagnosis and management.

2.
Nucleic Acids Res ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587197

RESUMO

Gene fusions and their chimeric products are commonly linked with cancer. However, recent studies have found chimeric transcripts in non-cancer tissues and cell lines. Large-scale efforts to annotate structural variations have identified gene fusions capable of generating chimeric transcripts even in normal tissues. In this study, we present a bottom-up approach targeting population-specific chimeric RNAs, identifying 58 such instances in the GTEx cohort, including notable cases such as SUZ12P1-CRLF3, TFG-ADGRG7 and TRPM4-PPFIA3, which possess distinct patterns across different ancestry groups. We provide direct evidence for an additional 29 polymorphic chimeric RNAs with associated structural variants, revealing 13 novel rare structural variants. Additionally, we utilize the All of Us dataset and a large cohort of clinical samples to characterize the association of the SUZ12P1-CRLF3-causing variant with patient phenotypes. Our study showcases SUZ12P1-CRLF3 as a representative example, illustrating the identification of elusive structural variants by focusing on those producing population-specific fusion transcripts.

3.
ACS Appl Bio Mater ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581388

RESUMO

Carvedilol (CVD), an adrenoreceptor blocker, is a hydrophobic Biopharmaceutics Classification System class II drug with poor oral bioavailability due to which frequent dosing is essential to attain pharmacological effects. Quercetin (QC), a polyphenolic compound, is a potent natural antioxidant, but its oral dosing is restricted due to poor aqueous solubility and low oral bioavailability. To overcome the common limitations of both drugs and to attain synergistic cardioprotective effects, we formulated CVD- and QC-encapsulated cationic nanoliposomes (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. We designed CVD- and QC-loaded cationic nanoliposomal (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. In vitro drug release studies of CVD/QC-L.O.F. (16.25%) exhibited 18.78 ± 0.57% of QC release and 91.38 ± 0.93% of CVD release for 120 h. Ex vivo nasal permeation studies of CVD/QC-L.O.F. demonstrated better permeation of QC (within 96 h), i.e., 75.09% compared to in vitro drug release, whereas CVD permeates within 48 h, indicating the better interaction between cationic NLPs and the negatively charged biological membrane. The developed nasal gel showed a sufficient mucoadhesive property, good spreadability, higher firmness, consistency, and cohesiveness, indicating suitability for membrane application and intranasal administration. CVD-NLPs, QC-NLPs, and CVD/QC-NLPs were evaluated for in vitro cytotoxicity, in vitro ROS-induced cell viability assessment, and a cellular uptake study using H9c2 rat cardiomyocytes. The highest in vitro cellular uptake of CVD/QC-cationic NLPs by H9c2 cells implies the benefit of QC loading within the CVD nanoliposomal carrier system and gives evidence for better interaction of NLPs carrying positive charges with the negatively charged biological cells. The in vitro H2O2-induced oxidative stress cell viability assessment of H9c2 cells established the intracellular antioxidant activity and cardioprotective effect of CVD/QC-cationic NLPs with low cytotoxicity. These findings suggest the potential of cationic NLPs as a suitable drug delivery carrier for CVD and QC combination for the intranasal route in the treatment of various cardiovascular diseases like hypertension, angina pectoris, etc. and for treating neurodegenerative disorders.

4.
Cureus ; 16(3): e55802, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586670

RESUMO

There are two significant groups of infection regarding ascitic fluid: spontaneous bacterial peritonitis (SBP) and culture-negative neutrocytic ascites (CNNA). SBP and CNNA typically occur in patients with cirrhosis. A 46-year-old male with end-stage biventricular heart failure presented with a heart failure exacerbation. He was treated with intravenous diuretics with the improvement of hypervolemia. He remained hospitalized to undergo an evaluation for tricuspid valve repair, but given the severity of his bi-ventricular heart failure, he underwent a heart transplant evaluation. As part of the work-up, he underwent an abdominal ultrasound that was significant for severe ascites but did not note an abnormal hepatic architecture suggestive of cirrhosis. A liver biopsy was then performed, which confirmed no evidence of cirrhosis. His hospitalization was complicated by refractory cardiac ascites, which required a bi-weekly paracentesis. The serum albumin-ascites gradient (SAAG) from his initial paracentesis was 1.4, indicating the etiology was from portal hypertension. The total protein was greater than 2.5 in multiple studies, so the etiology was less concerning for cirrhosis and secondary to his heart failure. About two weeks into his hospital course, he developed a leukocytosis but remained hemodynamically stable and asymptomatic from an infectious standpoint. Analysis of his ascitic fluid initially was negative for infection, but he later developed an elevated total neutrophil count on a subsequent ascitic fluid analysis study. The body fluid culture remained negative for bacterial growth. Hepatology was consulted, and he met the criteria for CNNA, so treatment with ceftriaxone was initiated. After initiating antibiotics, his leukocytosis and elevated ascitic fluid total neutrophil count resolved. Ascitic infections such as CNNA generally occur in patients with liver cirrhosis but may occur in patients without cirrhosis, as observed in our patient. This case highlights that patients with cardiac ascites can develop ascitic fluid infections that may have an impact on their mortality. The precipitating factor that enabled the patient to develop CNNA is unclear but may be related to the translocation of bacteria during his congestive heart failure exacerbation. Although uncommon in a patient with cardiac ascites, an early diagnosis of CNNA and the initiation of antibiotics can be important in preventing patient mortality.

5.
Afr J Paediatr Surg ; 21(2): 144-147, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38546255

RESUMO

ABSTRACT: Cleft palate leads to difficulty in suckling, speech abnormalities, dental problems, hearing loss and middle ear infections. Feeding plate acts as a barrier between the oral and nasal cavities allowing the normal development of jaws and enhanced nutritional supply to the patient. Fabrication of the feeding plate using digital means provide better adaptability due to the engagement of all the possible favourable anatomic undercuts, thereby, providing better retention. This case report discusses the hybrid technique including both the digital and conventional means for fabrication of a feeding plate to obturate the defect between the oral and nasal cavity.


Assuntos
Fenda Labial , Fissura Palatina , Lactente , Humanos , Fissura Palatina/complicações , Fissura Palatina/cirurgia
6.
Polymers (Basel) ; 16(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38543448

RESUMO

Chemotherapy together with surgery and/or radiotherapy are the most common therapeutic methods for treating cancer. However, the off-target effects of chemotherapy are known to produce side effects and dose-limiting toxicities. Novel delivery platforms based on natural and synthetic polymers with enhanced pharmacokinetic and therapeutic potential for the treatment of cancer have grown tremendously over the past 10 years. Polymers can facilitate selective targeting, enhance and prolong circulation, improve delivery, and provide the controlled release of cargos through various mechanisms, including physical adsorption, chemical conjugation, and/or internal loading. Notably, polymers that are biodegradable, biocompatible, and physicochemically stable are considered to be ideal delivery carriers. This biomimetic and bio-inspired system offers a bright future for effective drug delivery with the potential to overcome the obstacles encountered. This review focuses on the barriers that impact the success of chemotherapy drug delivery as well as the recent developments based on natural and synthetic polymers as platforms for improving drug delivery for treating cancer.

7.
Cardiol Rev ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445894

RESUMO

Cardiovascular disease is the leading cause of death. In addition to the well-known risk factors associated with cardiovascular disease, such as age, diabetes mellitus, smoking, hypertension, and obesity, there has been a growing concern regarding cardiac complications stemming from the Gram-negative bacteria Helicobacter pylori. While H. pylori is most commonly associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma, it has also been implicated in extra gastric manifestations, encompassing cardiac, neurologic, ocular, and dermatologic issues. Key virulent factors for coronary artery disease include the vacuolating cytotoxin gene A and the cytotoxin-associated gene A. The most likely pathogenic mechanism of the relationship between H. pylori and coronary artery disease is initiating a chronic inflammatory process associated with infection and the modifications of classic risk factors. These alterations lead to the creation of prothrombotic and procoagulant environments. Here, we review the cardiac manifestations of H. pylori and the underlying pathophysiological mechanisms.

8.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396653

RESUMO

Endothelial cells line at the most inner layer of blood vessels. They act to control hemostasis, arterial tone/reactivity, wound healing, tissue oxygen, and nutrient supply. With age, endothelial cells become senescent, characterized by reduced regeneration capacity, inflammation, and abnormal secretory profile. Endothelial senescence represents one of the earliest features of arterial ageing and contributes to many age-related diseases. Compared to those in arteries and veins, endothelial cells of the microcirculation exhibit a greater extent of heterogeneity. Microcirculatory endothelial senescence leads to a declined capillary density, reduced angiogenic potentials, decreased blood flow, impaired barrier properties, and hypoperfusion in a tissue or organ-dependent manner. The heterogeneous phenotypes of microvascular endothelial cells in a particular vascular bed and across different tissues remain largely unknown. Accordingly, the mechanisms underlying macro- and micro-vascular endothelial senescence vary in different pathophysiological conditions, thus offering specific target(s) for therapeutic development of senolytic drugs.


Assuntos
Células Endoteliais , Doenças Vasculares , Humanos , Células Endoteliais/fisiologia , Microcirculação/fisiologia , Envelhecimento , Senescência Celular/fisiologia
9.
bioRxiv ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38405903

RESUMO

RNA processing mechanisms, such as alternative splicing and RNA editing, have been recognized as critical means to expand the transcriptome. Chimeric RNAs formed by intergenic splicing provide another potential layer of RNA diversification. By analyzing a large set of RNA-Seq data and validating results in over 1,200 blood samples, we identified UBA1-CDK16 , a female-specific chimeric transcript. Intriguingly, both parental genes, are expressed in males and females. Mechanistically, UBA1-CDK16 is produced by cis-splicing between the two adjacent X-linked genes, originating from the inactive X chromosome. A female-specific chromatin loop, formed between the junction sites, facilitates the alternative splicing of its readthrough precursor. This unique chimeric transcript exhibits evolutionary conservation, evolving to be female-specific from non-human primates to humans. Furthermore, our investigation reveals that UBA1-CDK16 is enriched in the myeloid lineage and plays a regulatory role in myeloid differentiation. Notably, female COVID-19 patients who tested negative for this chimeric transcript displayed higher counts of neutrophils, highlighting its potential role in disease pathogenesis. These findings support the notion that chimeric RNAs represent a new repertoire of transcripts that can be regulated independently from the parental genes, and a new class of RNA variance with potential implications in sexual dimorphism and immune responses.

10.
Am Heart J ; 270: 86-94, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38309610

RESUMO

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).


Assuntos
Estenose da Valva Aórtica , Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Substituição da Valva Aórtica Transcateter , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Valva Aórtica/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Ponte de Artéria Coronária , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Resultado do Tratamento
11.
Curr Probl Cardiol ; 49(4): 102439, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301917

RESUMO

BACKGROUND: Rising incidence of heart failure (HF) in the Western world despite advanced clinical care necessitate exploration of further preventive tools and strategies. Lipoprotein(a) [Lp(a)], recognized as one of the major cardiovascular risk factors has also been implicated as a risk factor for HF. However, existing evidence remains inconclusive and that has led us to perform this meta-analysis. METHODS: PubMed/Medline, EMBASE and Scopus were systematically searched for studies evaluating an association of Lp(a) with occurrence of HF from inception-till November 2023. Random effects models and I2 statistics were used for pooled odds ratio (OR) and heterogeneity assessment. We performed leave one out sensitivity analyses by sequentially removing one study at a time and recalculating the pooled effect size. RESULT: Our search rendered in total 360 studies and after final screening this resulted in 7 Mendelian randomization (MR) design. According to the MR analysis, increasing Lp(a) level were significantly associated with increased risk of HF (OR 1.064, 95 % CI: 1.043-1.086, I2= 97.59 %, P < 0.001). In addition, Leave-one-out sensitivity analysis showed that the effect size did not change substantially by removal of any particular study in MR studies and ORs ranged from 1.051 (when excluding Levin) to a maximum of 1.111 (when excluding Wang or Jiang), hereby confirming the association. CONCLUSION: We were able to show that by meta-analysis of MR data, increasing lipoprotein (a) levels are associated with an increased risk of HF. Whether this is due to a direct effect on heart muscle contraction or whether this is due to an increased risk of ischemic cardiac disease remains to be elucidated.


Assuntos
Doença da Artéria Coronariana , Insuficiência Cardíaca , Humanos , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/genética , Lipoproteína(a)/genética , Análise da Randomização Mendeliana
12.
Nanoscale ; 16(7): 3510-3524, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38265458

RESUMO

Herein, inspired by Acacia auriculiformis fruit, the shish-kebab-like growth of ZnO on carbon urchin (ZnO@CU) was designed using microwave radiation, thus leading to a hierarchal 3D structure that can promote multiple internal reflections through polarization centers. This hierarchal structure was then dispersed in a designer polyetherimide (PEI) matrix containing dynamic covalent bonds that can undergo metathesis, triggered by temperature, to harness self-healing properties in the composite. Such key attributes are required for their potential use in EMI shielding applications where frequent repairs are indispensable. Morphological investigation revealed that the ZnO flower was periodically nucleated like 'shish-kebab' structures on CU surfaces. CU was designed from short carbon fibers using a facile modified method. The EMI shielding performance of the resulting composites was investigated in the X-band, illustrating a shielding effectiveness of -40.6 dB for 2 wt% of ZnO@CU loading, and the composite can be preserved after the self-healing procedure. The ZnO 'kebabs' on 'CU shish' facilitated multiple scattering and numerous polarization centers to improve the EMI shielding performances at extremely low filler contents. In addition, the mechanical and thermal properties of the composite showed improved structural integrity and superior resistance to extreme temperatures, respectively. Overall, the proposed ZnO@CU/PEI composite has great potential to fulfill the increasing demands for lightweight EMI shielding materials in many fields.

13.
Colloids Surf B Biointerfaces ; 234: 113745, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38241890

RESUMO

Recent efforts have focused on developing improved drug delivery systems with enhanced therapeutic efficacy and minimal side effects. Micelles, self-assembled from amphiphilic block copolymers in aqueous solutions, have gained considerable attention for drug delivery. However, there is a need to further enhance their efficiency. These micelles offer benefits like biodegradability, biocompatibility, sustained drug release, and improved patient compliance. Yet, researchers must address stability issues and reduce toxicity. Nanoscale self-assembled structures have shown promise as efficient drug carriers, offering an alternative to conventional methods. Fine-tuning at the monomeric and molecular levels, along with structural modifications, is crucial for optimal drug release profiles. Various strategies, such as entrapping hydrophobic drugs and using polyethylene oxide diblock copolymer micelles to resist protein adsorption and cellular adhesion, protect the hydrophobic core from degradation. The polyethylene oxide corona also provides stealth properties, prolonging blood circulation for extended drug administration. Amphiphilic copolymers are attractive for drug delivery due to their adjustable properties, allowing control over micelle size and morphology. Emerging tools promise complex and multifunctional platforms. This article summarizes about the challenges as far as the use of micelles is concerned, including optimizing performance, rigorous pre-clinical and clinical research, and suggests further improvement for drug delivery efficacy.


Assuntos
Sistemas de Liberação de Medicamentos , Micelas , Humanos , Polietilenoglicóis/química , Portadores de Fármacos/química , Polímeros/química
14.
Clin. transl. oncol. (Print) ; 26(1): 1-15, jan. 2024.
Artigo em Inglês | IBECS | ID: ibc-229143

RESUMO

MicroRNAs (miRNAs) negatively affect gene expression by binding to their specific mRNAs resulting in either mRNA destruction or translational repression. The aberrant expression of various miRNAs has been associated with a number of human cancer. Oncogenic or tumor-suppressor miRNAs regulate a variety of pathways involved in the development of breast cancer (BC), including cell proliferation, apoptosis, metastasis, cancer recurrence, and chemoresistance. Variations in miRNA-encoding genes and their target genes lead to dysregulated gene expression resulting in the development and progression of BC. The various therapeutic approaches to treat the disease include chemotherapy, radiation therapy, surgical removal, hormone therapy, chemotherapy, and targeted biological therapy. The purpose of the current review is to explore the genetic variations in tumor-suppressor miRNA-encoding genes and their target genes in association with the disease development and prognosis. The therapeutic interventions targeting the variants for better disease outcomes have also been discussed (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Regulação Neoplásica da Expressão Gênica , Variação Genética , Genes Supressores de Tumor , MicroRNAs/genética , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/genética
15.
NPJ Precis Oncol ; 8(1): 11, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38225404

RESUMO

Circular RNAs (circRNAs) are a family of endogenous RNAs that have become a focus of biological research in recent years. Emerging evidence has revealed that circRNAs exert biological functions by acting as transcriptional regulators, microRNA sponges, and binding partners with RNA-binding proteins. However, few studies have identified coding circRNAs, which may lead to a hidden repertoire of proteins. In this study, we unexpectedly discovered a protein-encoding circular RNA circCCDC7(15,16,17,18,19) while we were searching for prostate cancer related chimeric RNAs. circCCDC7(15,16,17,18,19) is derived from exon 19 back spliced to exon 15 of the CCDC7 gene. It is significantly downregulated in patients with high Gleason score. Prostate cancer patients with decreased circCCDC7(15,16,17,18,19) expression have a worse prognosis, while linear CCDC7 had no such association. Overexpressed circCCDC7(15,16,17,18,19) inhibited prostate cancer cell migration, invasion, and viability, supporting classification of circCCDC7(15,16,17,18,19) as a bona fide tumor suppressor gene. We provide evidence that its tumor suppressive activity is driven by the protein it encodes, and that circCCDC7(15,16,17,18,19) encodes a secretory protein. Consistently, conditioned media from circCCDC7(15,16,17,18,19) overexpressing cells has the same tumor suppressive activity. We further demonstrate that the tumor suppressive activity of circCCDC7(15,16,17,18,19) is at least partially mediated by FLRT3, whose expression also negatively correlates with Gleason score and clinical prognosis. In conclusion, circCCDC7(15,16,17,18,19) functions as a tumor suppressor in prostate cancer cells through the circCCDC7-180aa secretory protein it encodes, and is a promising therapeutic peptide for prostate cancer.

16.
Heliyon ; 10(1): e23736, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38268586

RESUMO

The role of higher education in the foreign policy of states has been increasing significantly in order to generate soft power. Nevertheless, the literature on the educational aspect of soft power has yet to be systematically reviewed. Therefore, this systematic review is conducted to delineate and analyze the major studies in the field of international higher education which indicates education as a soft power resource for a country. To identify the multiple and contrary arguments on the topic, this study reviewed 48 peer-reviewed articles published from 2001 to 2022. The data collected from the reviewed papers are organized into five sub-sections outlined in the results sections. The contradictions in the literature are examined within the sub-sections in order to understand the various perspectives on education as a resource of soft power. Through analyzing the data mentioned in the results section, this study provides a framework of the essential conditions to harness education as a soft power resource. Furthermore, this review also suggests prospects for future research in this area.

17.
Clin Transl Oncol ; 26(1): 1-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37093457

RESUMO

MicroRNAs (miRNAs) negatively affect gene expression by binding to their specific mRNAs resulting in either mRNA destruction or translational repression. The aberrant expression of various miRNAs has been associated with a number of human cancer. Oncogenic or tumor-suppressor miRNAs regulate a variety of pathways involved in the development of breast cancer (BC), including cell proliferation, apoptosis, metastasis, cancer recurrence, and chemoresistance. Variations in miRNA-encoding genes and their target genes lead to dysregulated gene expression resulting in the development and progression of BC. The various therapeutic approaches to treat the disease include chemotherapy, radiation therapy, surgical removal, hormone therapy, chemotherapy, and targeted biological therapy. The purpose of the current review is to explore the genetic variations in tumor-suppressor miRNA-encoding genes and their target genes in association with the disease development and prognosis. The therapeutic interventions targeting the variants for better disease outcomes have also been discussed.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Genes Supressores de Tumor , Variação Genética , Regulação Neoplásica da Expressão Gênica
18.
Microbiol Res ; 279: 127553, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38007891

RESUMO

The plant rhizosphere is regarded as a microbial hotspot due to a wide array of root exudates. These root exudates comprise diverse organic compounds such as phenolic, polysaccharides, flavonoids, fatty acids, and amino acids that showed chemotactic responses towards microbial communities and mediate significant roles in root colonization. The rhizospheric microbiome is a crucial driver of plant growth and productivity, contributing directly or indirectly by facilitating nutrient acquisition, phytohormone modulation, and phosphate solubilization under normal and stressful conditions. Moreover, these microbial candidates protect plants from pathogen invasion by secreting antimicrobial and volatile organic compounds. To enhance plant fitness and yield, rhizospheric microbes are frequently employed as microbial inoculants. However, recent developments have shifted towards targeted rhizosphere engineering or microbial recruitments as a practical approach to constructing desired plant rhizospheres for specific outcomes. The rhizosphere, composed of plants, microbes, and soil, can be modified in several ways to improve inoculant efficiency. Rhizosphere engineering is achieved through three essential mechanisms: a) plant-mediated modifications involving genetic engineering, transgenics, and gene editing of plants; b) microbe-mediated modifications involving genetic alterations of microbes through upstream or downstream methodologies; and c) soil amendments. These mechanisms shape the rhizospheric microbiome, making plants more productive and resilient under different stress conditions. This review paper comprehensively summarizes the various aspects of rhizosphere engineering and their potential applications in maintaining plant health and achieving optimum agricultural productivity.


Assuntos
Raízes de Plantas , Rizosfera , Agricultura/métodos , Plantas , Solo/química , Microbiologia do Solo
19.
Prostate Cancer Prostatic Dis ; 27(1): 109-115, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37620427

RESUMO

BACKGROUND: Management of urinary symptoms in elderly patients with benign prostatic hyperplasia (BPH) is complex given challenges with medications and invasive surgeries. Rezum, a minimally invasive water vapor therapy, is an emerging alternative. We compare real-world Rezum outcomes between young and elderly patients over 4 years. METHODS: We retrospectively analyzed a multiethnic population treated with Rezum at a single center between 2017-2019. Patients were stratified into young (<65 years) or elderly (≥65 years) cohorts. International Prostate Symptom Score (IPSS), Quality of Life (QoL), maximum urinary flow rate (Qmax), decisional regret scores, and adverse events (AEs) were assessed at baseline, 1-, 3-, 6-, 12-, and/or 48-months. Descriptive statistics were compared using t-tests, Chi-squared, or Mann-Whitney U tests. Changes in outcomes were assessed using Wilcoxon signed-rank tests, stratified by age. RESULTS: 256 patients - 146 (57%) young and 110 (43%) elderly - were included. The majority were Asian (33.2%) or non-Hispanic Black (28.9%). Significant improvements were observed in the combined cohort at 4-years in IPSS, QoL, and Qmax when compared to baseline (all p < 0.05). Between the age cohorts, there were no significant differences in IPSS, QoL, or Qmax at any follow-up. Within both cohorts, significant improvements in IPSS and QoL were found from baseline to all follow-ups. In the young cohort, Qmax was significantly improved from baseline to all follow-ups while in the elderly cohort, this was observed only at the 3-month follow-up. No significant differences in AEs or regret was found between cohorts. There was no significant difference in 4-year surgical retreatment rates between cohorts (elderly 4.0% vs young 4.4%, p = 0.86). CONCLUSIONS: There were no significant differences in IPSS, QoL, or AEs between elderly and younger men over 4 years following Rezum, suggesting comparable benefits and risks. Future research is warranted to clarify the impact of Rezum on Qmax in elderly men.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , Idoso , Qualidade de Vida , Sintomas do Trato Urinário Inferior/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Hiperplasia Prostática/cirurgia
20.
Curr Probl Cardiol ; 49(1 Pt A): 102024, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37553064

RESUMO

Lipoprotein (a) (Lp[a]) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, data on association of Lp(a) with risk of atrial fibrillation (AF) is still limited. We searched PubMed/Medline, Scopus, and EMBASE for studies evaluating the association of Lp(a) with the occurrence of AF until July 2023. Random effects models and I2 statistics were used for pooled odds ratios (OR), and heterogeneity assessments. A subgroup analysis was performed based on the cohort population, and a one-out sensitivity analysis was performed. This meta-analysis comprised 275,647 AF cases and 2,100,172 Lp(a) participants. An increase in Lp(a) was associated with an increased risk of AF in mendelian randomization (MR) studies (OR 1.024, 95% CI: 1.007-1.042, I2 = 87.72%, P < 0.001). Leave-one-out sensitivity analysis confirmed equivalent results in MR studies. Subgroup analysis of MR studies revealed a higher risk of AF in the European cohort (OR 1.023, 95% CI: 1.007-1.040, I2 = 89.05%, P < 0.001) and a low risk (OR 0.940, 95% CI: 0.893-0.990) in the Chinese population. Meta-analysis of the MR data suggested higher levels of Lp(a) were associated with increased risk of AF. Future robust prospective studies are warranted to validate these findings.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Lipoproteína(a)/genética , Análise da Randomização Mendeliana , Estudos Prospectivos , Fatores de Risco
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