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1.
Cell Signal ; : 111410, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39270918

RESUMEN

Angiotensin II receptors, Type 1 (AT1R) and Type 2 (AT2R) are 7TM receptors that play critical roles in both the physiological and pathophysiological regulation of the cardiovascular system. While AT1R blockers (ARBs) have proven beneficial in managing cardiac, vascular and renal maladies they cannot completely halt and reverse the progression of pathologies. Numerous experimental and animal studies have demonstrated that ß-arrestin biased AT1R-ligands (such as SII-AngII, S1I8, TRV023, and TRV027) offer cardiovascular benefits by blocking the G protein signaling while retaining the ß-arrestin signaling. However, these ligands failed to show improvement in heart-failure outcome over the placebo in a phase IIb clinical trial. One major limitation of current ß-arrestin biased AT1R-ligands is that they are peptides with short half-lives, limiting their long-term efficacy in patients. Additionally, ß-arrestin biased AT1R-ligand peptides, may inadvertently block AT2R, a promiscuous receptor, potentially negating its beneficial effects in post-myocardial infarction (MI) patients. Therefore, developing a small molecule ß-arrestin biased AT1R-ligand with a longer half-life and specificity to AT1R could be more effective in treating heart failure. This approach has the potential to revolutionize the treatment of cardiovascular diseases by offering more sustained and targeted therapeutic effects.

2.
Plant Methods ; 20(1): 122, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135113

RESUMEN

Virus-Induced Gene Silencing (VIGS) is a versatile tool in plant science, yet its application to non-model species like sunflower demands extensive optimization due to transformation challenges. In this study, we aimed to elucidate the factors that significantly affect the efficiency of Agrobacterium-VIGS in sunflowers. After testing a number of approaches, we concluded that the seed vacuum technique followed by 6 h of co-cultivation produced the most efficient VIGS results. Genotype-dependency analysis revealed varying infection percentages (62-91%) and silencing symptom spreading in different sunflower genotypes. Additionally, we explored the mobility of tobacco rattle virus (TRV) and phenotypic silencing manifestation (photo-bleaching) across different tissues and regions of VIGS-infected sunflower plants. We showed the presence of TRV is not necessarily limited to tissues with observable silencing events. Finally, time-lapse observation demonstrated a more active spreading of the photo-bleached spots in young tissues compared to mature ones. This study not only offers a robust VIGS protocol for sunflowers but also provides valuable insights into genotype-dependent responses and the dynamic nature of silencing events, shedding light on TRV mobility across different plant tissues.

3.
J Clin Med ; 13(13)2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38999428

RESUMEN

Introduction: Benign paroxysmal positional vertigo (BPPV) stands as the most common cause of peripheral vertigo. Its treatment with repositioning maneuvers on an examination table is highly effective. However, patients with back or neck problems, paraplegia, or other conditions face challenges with these maneuvers, potentially experiencing longer healing times and creating additional difficulties for physicians diagnosing and treating BPPV in everyday practice. The emergence of mechanical rotational chairs (MRCs) offers a more convenient alternative for performing these maneuvers. Objectives: The primary objective was to compare the effectiveness of maneuvers on the examination table with those on MRCs in BPPV patients diagnosed in the emergency room and randomly classified into one of the treatment options. The secondary objectives included a comparison of patient quality of life during BPPV episodes and after their resolution and an analysis of recurrences and associated risk factors. Methods: This was a cohort study on sixty-three patients diagnosed with BPPV in the emergency department. Patients were classified into two cohorts depending on diagnostic and treatment maneuvers (MRC or conventional repositioning maneuvers (CRMs)) and received weekly follow-ups until positioning maneuvers became negative. Subsequent follow-ups were conducted at 1 month, 3 months, and 6 months after the resolution of vertigo. Patients were classified into two groups based on their assigned treatment method. Results: Thirty-one patients were treated with CRMs and 32 with TRV. Mean age was 62.29 ± 17.67 years and the most affected canal was the PSC (96.8%). The mean number of required maneuvers was two, while 55.56% only required one maneuver until resolution. Recurrence was present in 26.98% of the patients during the 6-month follow-up. Comparing both cohorts, there were no statistically significant differences between treatments (TRV vs. CRM) regarding the number of maneuvers, number of recurrences, and days until remission of BPPV. Dizziness Handicap Inventory and Visual Analogue Scale values decreased considerably after BPPV resolution, with no statistically significant differences between the groups. Age was identified as a covariable in the number of maneuvers and days until BPPV resolution, showing that an increase in age implies a greater need of maneuvers. Conclusions: There was no difference between the means of treatment for BPPV in our population ot There was no difference between the groups of treatments for BPPV in our population. The quality of life of patients improved six months after the resolution of BPPV, regardless of the treatment applied.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39001924

RESUMEN

INTRODUCTION: A cupulolithiasis of the lateral semicircular canal is an accumulation of otolithic debris at the level of the cupula of the same canal. Its pathophysiology generally generates a specific clinical presentation. This situation can be very disabling for the patient and tricky to treat for the clinician. CASE REPORT: The patient was a 70-year-old man with cupulolithiasis of the right lateral semicircular canal. We present here the conversion of cupulolithiasis to canalolithiasis using the Thomas Richard Vitton (TRV) repositioning chair, as well as the treatment of this canalolithiasis through a mechanical liberation maneuver. CONCLUSION: The results of manual therapeutic maneuvers for Benign Paroxysmal Positional Vertigo (BPPV) are generally good regardless of the type of BPPV. It can sometimes be more challenging to resolve an ageotropic-type BPPV of the lateral semicircular canal and mechanically-assisted maneuvers using a repositioning chair may be required. Faced with symptom resistance despite attempts at multiple liberatory maneuvers, clinicians must be able to reconsider their initial diagnosis and investigate other potentially more serious origins of these symptoms. The TRV chair can be a treatment option in the management of cupulolithiasis, especially in cases where classic reduction maneuvers do not always yield good results.

5.
Biotechnol J ; 19(5): e2400204, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38797722

RESUMEN

Plant virus-based sgRNA delivery strategy has been widely applied for efficient genome editing across various plant species, leveraging its significant advantages in the rapid expression and expansion of sgRNA through virus replication and movement. However, the efficacy of the virus-induced gene editing (VIGE) tool in tomato has yet to be explored. In this paper, we established a TRV-mediated CRISPR/Cas9 genome editing system in the somatic cells of tomato, reporting the validation of VIGE and evaluating the mutagenesis efficiency in both tomato leaves and fruits using high-throughput sequencing. The results demonstrated an approximate 65% efficiency of VIGE in tomato leaves for the selected target genes, with VIGE efficiency reaching up to 50% in tomato fruits. This research not only introduces an efficient tool for reverse genetics but also reveals substantial potential of VIGE in surpassing traditional tissue culture techniques for creating heritable mutations in tomato.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Virus de Plantas , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/virología , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , Virus de Plantas/genética , Hojas de la Planta/genética , Hojas de la Planta/virología , Genoma de Planta/genética , Frutas/genética , Frutas/virología , Plantas Modificadas Genéticamente/genética
6.
Vaccine ; 42(18): 3916-3929, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38782665

RESUMEN

Nonenveloped virus-like particles (VLPs) are self-assembled oligomeric structures composed of one or more proteins that originate from diverse viruses. Because these VLPs have similar antigenicity to the parental virus, they are successfully used as vaccines against cognate virus infection. Furthermore, after foreign antigenic sequences are inserted in their protein components (chimVLPs), some VLPs are also amenable to producing vaccines against pathogens other than the virus it originates from (these VLPs are named platform or epitope carrier). Designing chimVLP vaccines is challenging because the immunogenic response must be oriented against a given antigen without altering stimulant properties inherent to the VLP. An important step in this process is choosing the location of the sequence modifications because this must be performed without compromising the assembly and stability of the original VLP. Currently, many immunogenic data and computational tools can help guide the design of chimVLPs, thus reducing experimental costs and work. In this study, we analyze the structure of a novel VLP that originate from an insect virus and describe the putative regions of its three structural proteins amenable to insertion. For this purpose, we employed molecular dynamics (MD) simulations to assess chimVLP stability by comparing mutated and wild-type (WT) VLP protein trajectories. We applied this procedure to design a chimVLP that can serve as a prophylactic vaccine against the SARS-CoV-2 virus. The methodology described in this work is generally applicable for VLP-based vaccine development.


Asunto(s)
Epítopos , Vacunas de Partículas Similares a Virus , Vacunas de Partículas Similares a Virus/inmunología , Epítopos/inmunología , Epítopos/genética , Humanos , SARS-CoV-2/inmunología , Simulación de Dinámica Molecular , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Biología Computacional/métodos
7.
Gene ; 913: 148385, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38493973

RESUMEN

Juglans sigillata Dode is one of the important tree species in southwest China, and it has significant economic and ecological value. However, there is still a lack of effective methods to identify the functional genes of J. sigillata. By verifying the model plant tobacco, the pTRV2::JsPDS vector was able to cause photobleaching. This study showed that photobleaching occurred 24 and 30 d after the silencing vector was infected with aseptic seedlings and fruits of J. sigillata, respectively. When the OD600 was 0.6, and the injection dose was 500 µL, the gene silencing efficiency of aseptic seedlings was the highest at 16.7 %, significantly better than other treatments. Moreover, when the OD600 was 0.8, and the injection dose was 500 µL, the gene silencing efficiency in the walnut fruit was the highest (20 %). In addition, the VIGS system was successfully used to silence JsFLS2 and JsFLS4 genes in J. sigillata. This study also showed that the flavonol content and gene expression in the treatment group were decreased compared to the control group. In addition, the proteins transcribed and translated from the JsFLS4 gene may have higher catalytic activity for dihydroquercetin. The above results indicate that the TRV-mediated VIGS system can be an ideal tool for studying J. sigillata gene function.


Asunto(s)
Juglans , Virus de Plantas , Juglans/genética , Silenciador del Gen , Fenotipo , Frutas , Nicotiana , Plantones/genética , Regulación de la Expresión Génica de las Plantas , Virus de Plantas/genética
8.
J Thorac Dis ; 16(1): 51-64, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38410615

RESUMEN

Background: Transthoracic echocardiography (TTE) is recommended as the most important noninvasive screening tool for the diagnosis of pulmonary hypertension (PH), sonographers usually measure the volume of regurgitant flow rather than evaluating the spectral quality, so physicians will determine whether the ultrasound measurements of pulmonary arterial systolic pressure (US-PASP) are reliable based on the volume of tricuspid regurgitation (TR). Therefore, for the first time, we grade the quality of TR spectrum (TRS) based on its integrity and clarity, aiming to assess clinical application value of different tricuspid regurgitant spectrum quality grades (TR-SQG), and investigate whether the accuracy of US-PASP is more trustworthy than TR. Methods: We retrospectively analyzed 108 patients with chronic thromboembolic PH (CTEPH) to compare the correlation and agreement between US-PASP and right heart catheterization measurements of PASP (RHC-PASP). TR area (TRA) and TRS were measured in each patient, and TR-SQG was performed. Results: The correlation coefficients between US-PASP and RHC-PASP were r=0.622 (P<0.001), r=0.754 (P<0.001), r=0.595 (P<0.001) in mild, moderate, severe TR, and r=0.301 (P=0.135), r=0.747 (P<0.001), r=0.739 (P<0.001), r=0.828 (P<0.001) in TR-SQG I-IV, respectively. Bland-Altman analysis revealed the mean biases of 5.05, 3.06, 7.62 mmHg in mild, moderate, severe TR, and -16.47, -8.07, 1.82, 6.09 mmHg in TR-SQG I-IV, respectively. In mild TR with the TR-SQG III and IV, the correlation coefficients between US-PASP and RHC-PASP were r=0.779 (P<0.001), intraclass correlation coefficient (ICC) =0.774, paired t-test P=0.160, respectively; and the consistency was significantly higher than that of mild TR without considering TR-SQG. In moderate TR with the TR-SQG III and IV, the r=0.749, ICC =0.746, paired t-test P=0.298 between US-PASP and RHC-PASP. Conclusions: The US-PASP with TR-SQG III or IV is trustworthy, and its accuracy and consistency are better than those predicted by the traditional severity of TR. The establishment of the ultrasound evaluation system of TR-SQG helps clinicians to judge whether the US-PASP is accurate, credible, and reliable.

9.
Methods Mol Biol ; 2724: 273-288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37987913

RESUMEN

Gene editing using clustered, regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) nuclease is an excellent tool for assessing gene function in plants. However, delivery of CRISPR/Cas-editing components into plant cells is still a major bottleneck and requires tissue culture-based approaches and regeneration of plants. To overcome this limitation, several plant viral vectors have recently been engineered to deliver single-guide RNA (sgRNA) targets into SpCas9-expressing plants. Here, we describe an optimized, step-by-step protocol based on the tobacco rattle virus (TRV)-based vector system to deliver sgRNAs fused to mobile tRNA sequences for efficient heritable editing in Nicotiana benthamiana and Arabidopsis thaliana model systems. The protocol described here could be adopted to study the function of any gene of interest.


Asunto(s)
Arabidopsis , ARN Guía de Sistemas CRISPR-Cas , Edición Génica , Nicotiana/genética , Arabidopsis/genética , Endonucleasas
10.
Plants (Basel) ; 12(17)2023 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-37687408

RESUMEN

The recent availability of a number of tea plant genomes has sparked substantial interest in using reverse genetics to explore gene function in tea (Camellia sinensis). However, a hurdle to this is the absence of an efficient transformation system, and virus-induced gene silencing (VIGS), a transient transformation system, could be an optimal choice for validating gene function in the tea plant. In this study, phytoene desaturase (PDS), a carotenoid biosynthesis gene, was used as a reporter to evaluate the VIGS system. The injection sites of the leaves (leaf back, petiole, and stem) for infiltration were tested, and the results showed that petiole injection had the most effective injection, without leading to necrotic lesions that cause the leaves to drop. Tea leaves were inoculated with Agrobacterium harboring a tobacco rattle virus plasmid (pTRV2) containing a CsPDS silencing fragment. The tea leaves exhibited chlorosis symptoms 7-14 days after inoculation, depending on the cultivar. In the chlorosis plants, the coat protein (CP) of tobacco rattle virus (TRV) was detected and coincided with the lower transcription of CsPDS and reduced chlorophyll content compared with the empty vector control, with 81.82% and 54.55% silencing efficiency of 'LTDC' and 'YSX', respectively. These results indicate that the VIGS system with petiole injection could quickly and effectively silence a gene in tea plants.

11.
Regul Toxicol Pharmacol ; 144: 105487, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37640100

RESUMEN

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 µg Cd/g creatinine for females aged 50-60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 µg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21-0.36 µg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63-1.8 µg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints.


Asunto(s)
Cadmio , Exposición a Riesgos Ambientales , Femenino , Animales , Humanos , Persona de Mediana Edad , Cadmio/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Valores de Referencia , Alimentos , Riñón
12.
Plant Cell Environ ; 46(11): 3592-3610, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37551976

RESUMEN

Control of plant virus diseases largely depends on the induced plant defence achieved by the external application of synthetic chemical inducers with the ability to modify defence-signalling pathways. However, most of the molecular mechanisms underlying these chemical inducers remain unknown. Here, we developed a chitosan-coated lentinan-loaded hydrogel and discovered how it protects plants from different virus infections. The hydrogel was synthesized by coating chitosan on the surface of the calcium alginate-lentinan (LNT) hydrogel (SL-gel) to form a CSL-gel. CSL-gels exhibit the capacity to prolong the stable release of lentinan and promote Ca2+ release. Application of CSL-gels on the root of plants induces broad-spectrum resistance against plant viruses (TMV, TRV, PVX and TuMV). RNA-seq analysis identified that Nicotiana benthamiana calmodulin-like protein gene 3 (NbCML3) is upregulated by the sustained release of Ca2+ from the CSL-gel, and silencing and overexpression of NbCML alter the susceptibility and resistance of tobacco to TMV. Our findings provide evidence that this novel and synthetic CSL-gel strongly inhibits the infection of plant viruses by the sustainable release of LNT and Ca2+ . This study uncovers a novel mode of action by which CSL-gels trigger NbCML3 expression through the stable and sustained release of Ca2+ .

13.
Molecules ; 28(14)2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37513355

RESUMEN

The AT1 receptor has mainly been associated with the pathological effects of the renin-angiotensin system (RAS) (e.g., hypertension, heart and kidney diseases), and constitutes a major therapeutic target. In contrast, the AT2 receptor is presented as the protective arm of this RAS, and its targeting via specific agonists is mainly used to counteract the effects of the AT1 receptor. The discovery of a local RAS has highlighted the importance of the balance between AT1/AT2 receptors at the tissue level. Disruption of this balance is suggested to be detrimental. The fine tuning of this balance is not limited to the regulation of the level of expression of these two receptors. Other mechanisms still largely unexplored, such as S-nitrosation of the AT1 receptor, homo- and heterodimerization, and the use of AT1 receptor-biased agonists, may significantly contribute to and/or interfere with the settings of this AT1/AT2 equilibrium. This review will detail, through several examples (the brain, wound healing, and the cellular cycle), the importance of the functional balance between AT1 and AT2 receptors, and how new molecular pharmacological approaches may act on its regulation to open up new therapeutic perspectives.


Asunto(s)
Sistema Cardiovascular , Hipertensión , Humanos , Sistema Renina-Angiotensina/fisiología , Sistema Cardiovascular/metabolismo , Hipertensión/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Angiotensina II/metabolismo
14.
Front Plant Sci ; 14: 1100416, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37035068

RESUMEN

Candidate genes (CG) for Botrytis cinerea resistance described in literature were mapped on gerbera linkage maps for which several QTL for Botrytis resistance had been found previously using a rapid, low-cost platform for SNP genotyping. In total, 29 CGs were mapped in either of two mapping populations. Four CGs were mapped within the previous identified QTL intervals and three co-localized with QTL. Two of these CGs for resistance against B. cinerea, PG1 (polygalacturonase gene) and sit (sitiens, ABA-aldehyde oxidase gene) that mapped in QTL regions for the ray floret disease resistance test were studied in detail. Virus-induced gene silencing (VIGS) was used for gene function analysis to determine the CGs' role in gerbera resistance to Botrytis. Ray florets, of which the CGs were silenced, showed a significantly delayed growth of lesions upon Botrytis infection compared to controls. Combining QTL analysis, candidate gene mapping and VIGS showed to be an useful combination to identify possible causal genes and for understanding the molecular mechanisms of Botrytis resistance in gerbera. The two genes seem to act as partial S-genes and are likely among the determining genes leading to the variation observed for B. cinerea resistance in gerbera.

15.
Front Neurol ; 14: 1040701, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36779048

RESUMEN

Background: Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disease. Both therapeutic and diagnostic benefits with mechanical rotation chairs (MRCs) for management of BPPV have been reported. No previous studies have compared diagnostics in MRCs to traditional diagnostics on an examination bed. Objective: To investigate the agreement between BPPV diagnostics performed with an MRC and traditional diagnostics on an examination bed. Secondary objectives were to (1) examine if the two test modalities differ in diagnostic properties when diagnosing largely untreated patients referred from general practitioners (uncomplicated BPPV) compared to patients referred from private ENTs (complicated BPPV) and (2) examine whether impaired participant cooperation during Manual Diagnostics (MDs) alters agreement, sensitivity and specificity. Method: Prospective randomized clinical trial in which patients with a case history of BPPV were recruited by referrals from general practitioners, otorhinolaryngologists and other hospital departments in the Northern Region of Denmark. Participants underwent diagnostic examinations twice: once by traditional MDs on an examination bed and once with an MRC. Initial examiner and order of test modality were randomized. Examiners were blinded to each other's findings. Results: When testing the ability to diagnose BPPV, agreement between the two test modalities, was 0.83, Cohen's kappa 0.66. When comparing MD diagnostics to MRC diagnostics (set as gold standard diagnostics following test result interpretation), values for MDs were: sensitivity 71%, specificity 98%, Negative Predictive Value 73%, and Positive Predictive Value 97%. Agreement regarding BPPV subtype classification was found to be 0.71, and Cohen's kappa 0.58. Agreement when isolating the diagnosis to posterior canalolithiasis (p-CAN) was 0.89, Cohen's kappa 0.78. Conclusion: Diagnostics, aided by an MRC, are more sensitive than traditional manual BPPV diagnostics. The overall agreement level between test modalities was found to be weak to moderate. When isolating diagnostics to p-CAN, the level of agreement increased to "moderate-strong." Results also showed higher agreement between test modalities and a significantly higher negative predictive value for MDs when examining patients referred directly from General Practitioners following no- or a single treatment attempt. The diagnostic properties of MDs improved in patients with a higher degree of cooperation.

16.
Pharmacol Res Perspect ; 11(1): e01053, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36639940

RESUMEN

Angiotensin II analogue and ß-arrestin biased agonist TRV027 (Sarcosine1 , d-Alanine8 -Angiotensin (Ang) II; SD Ang II), developed by Trevena, Inc. in the early 2010s, brought hopes of a novel treatment for cardiovascular diseases, due to its ability to simultaneously cause signaling through the ß-arrestin signaling pathway, while antagonizing the pathophysiological effects of Ang II mediated by the AT1 receptor G protein signaling cascades. However, a phase II clinical trial of this agent revealed no significant benefit compared to placebo treatment. Using 125 I-Sarcosine1 , Isoleucine8 -Ang II (125 I-SI Ang II) radioligand receptor competition binding assays, we assessed the relative affinity of TRV027 compared to SI Ang II for liver AT1 receptors. We also compared radioiodinated TRV027 (125 I-SD Ang II) binding affinity for liver AT1 receptors with 125 I-SI Ang II. We found that despite its anticipated gain in metabolic stability, TRV027 and 125 I-SD Ang II had reduced affinity for the AT1 receptor compared with SI Ang II and 125 I-SI Ang II. Additionally, male-female comparisons showed that females have a higher AT1 receptor density, potentially attributed to tissue-dependent estrogen and progesterone effects. Peptide drugs have become more popular over the years due to their increased bioavailability, fast onset of action, high specificity, and low toxicity. Even though Trevena®'s biased agonist peptide TRV027 offered greater stability and potency compared to earlier AT1 R biased agonists, it failed its phase II clinical trial in 2016. Further refinements to AT1 R biased agonist peptides to improve affinity, as seen with SI Ang II, with better stability and bioavailability, has the potential to achieve the anticipated biased agonism.


Asunto(s)
Angiotensina II , Hígado , Receptor de Angiotensina Tipo 1 , Sarcosina , Animales , Femenino , Masculino , Ratas , Alanina/metabolismo , Angiotensina II/farmacología , beta-Arrestinas/metabolismo , Isoleucina/metabolismo , Hígado/metabolismo , Sarcosina/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo
17.
Methods Mol Biol ; 2606: 203-218, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36592318

RESUMEN

The CRISPR/Cas9 system is an extremely powerful tool for targeted mutagenesis in plants. However, plant genome editing relies on the labor-intensive plant regeneration method for generating gene-edited plants. To overcome this bottleneck, several virus-induced genome editing (VIGE) techniques have been developed. The VIGE system aims to induce targeted mutations in germ cells without plant regeneration. However, due to the delivery issues of a large Cas9 protein, scientists focus on developing a virus-mediated delivery system for guide RNA into Cas9-overproducing plants. Here, we describe how to induce heritable targeted mutations in a non-model plant, Nicotiana attenuata, using VIGE system. This method will be applied for manipulating the target genes in any plants that scientists are interested in.


Asunto(s)
Edición Génica , Nicotiana , Edición Génica/métodos , Nicotiana/genética , Sistemas CRISPR-Cas/genética , Plantas/genética , Genoma de Planta , Plantas Modificadas Genéticamente/genética
18.
Gene ; 852: 147054, 2023 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-36395971

RESUMEN

Blueberry (Vaccinium corymbosum L.), a woody perennial bush in the genus Vaccinium, is an economically important and popular fruit crop worldwide. Development the superior cultivars, which including excellent fruit traits, not only means higher yielding and economic efficiency, but also produce fruit that to meet the preferences of different consumers. Excavating fruit quality-related genes, studying their functions, and using transgenic or molecular-assisted breeding are beneficial to the development of excellent blueberry varieties. Genetic transformation is an excellent way to study the function of genes in plants, however, it is a labor-intensive and time-consuming process to genetically transform many woody plants, including blueberry. Virus-induced gene silencing (VIGS) provides an efficient approach to knock-down the expression of target genes for functional analysis. In this study, tobacco rattle virus induced genes silencing (TRV-VIGS) was established in blueberry fruits using the VcANS gene as a reporter. The silenced sector of the skin of blueberry fruits injected with pTRV2 (plasmid Tobacco Rattle Virus, TRV-RNA2)::VcANS remained green or white at 25 days after agroinfiltration. In agroinfiltrated materials, the VcANS transcript levels were much lower in fruits with phenotypic changes (delayed color change) than in those infiltrated with the pTRV2 empty vector. Silencing of VcANS also affected the expression of other genes involved in the anthocyanin synthesis pathway. The experimental results support that VcANS can be used as an effective marker gene for VIGS system. In addition, the TRV-VIGS system has been successfully established in blueberry fruits, which provided an effective verification method for functional identification of unknown genes in blueberry fruits.


Asunto(s)
Arándanos Azules (Planta) , Virus de Plantas , Silenciador del Gen , Arándanos Azules (Planta)/genética , Frutas/genética , Nicotiana/genética , Vectores Genéticos , Virus de Plantas/genética , Regulación de la Expresión Génica de las Plantas
19.
Audiol Neurootol ; 28(1): 1-5, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36316006

RESUMEN

INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) is one of the most common causes of peripheral vertigo and can manifest in different forms. Multicanal BPPV is rare and difficult to treat. TRV Chair is a method that offers diagnosis and treatment at the same time. The aim was to analyze the outcomes of treatment of multicanal BPPV by means of TRV Chair and compare those results with manual maneuvers. METHODS: Forty-nine subjects aged 26-73 and diagnosed with multicanal BPPV were included. Appropriate maneuvers were performed on affected canals either by TRV Chair or manually. The number of maneuvers required by TRV Chair and manual maneuver were analyzed and compared. RESULTS: The mean number of maneuvers performed until the treatment was completed in manual treatment group was 2.57 ± 1.03, and in TRV group, it was 2.25 ± 1.16. No significant difference was observed between the number of maneuvers performed in either group until the end of the treatment (p > 0.05). DISCUSSION/CONCLUSIONS: Neither TRV Chair nor manual maneuvers were superior to the other in the treatment of multicanal BPPV cases.


Asunto(s)
Vértigo Posicional Paroxístico Benigno , Posicionamiento del Paciente , Humanos , Vértigo Posicional Paroxístico Benigno/terapia , Vértigo Posicional Paroxístico Benigno/diagnóstico , Posicionamiento del Paciente/métodos , Resultado del Tratamiento , Canales Semicirculares
20.
Otolaryngol Pol ; 77(6): 31-36, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38706261

RESUMEN

<b><br>Introduction:</b> Vertigo is a subjective sensation of swaying, tilting, spinning, instability, or being off-balance [1]. The concept of vertigo is not a precise term due to the possibility of its being related to numerous variable, frequently co-occurring sensations as experienced by the patient. For this reason, diagnosing the origin of vertigo quite frequently poses a serious dilemma for physicians. Dizziness can be of peripheral or central origin. Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo and is currently considered to account for about 14-42% of all cases of vertigo, depending on the authors [2-4]. However, this figure may be underestimated due to frequent misdiagnoses.</br> <b><br>Aim:</b> The aim of this paper is to review the currently available international literature on the use of the TRV chair so as to assess its usefulness and effectiveness in the diagnostics and possibly subsequent treatment of BPPV and its components.</br> <b><br>Materials and methods:</b> Included in this literature review are peer-reviewed papers authored by various research teams as available in PubMed, Google Scholar, and Scopus databases.</br> <b><br>Results:</b> The TRV chair is helpful in precise diagnosis and subsequent treatment of BPPV subtypes (canalithiasis and cupulolithiasis) as well as in the evaluation of the number of affected canals, as shown in the papers analyzed in this review.</br> <b><br>Conclusions:</b> The use of TRV in the context of diagnosis and therapy of benign paroxysmal positional vertigo presents with potential for the improvement of diagnostic results, management protocols, and patients' quality of lives.</br>.


Asunto(s)
Vértigo Posicional Paroxístico Benigno , Humanos , Vértigo Posicional Paroxístico Benigno/diagnóstico , Vértigo Posicional Paroxístico Benigno/terapia , Vértigo/diagnóstico , Vértigo/terapia , Masculino , Femenino , Equilibrio Postural , Mareo/diagnóstico , Mareo/etiología , Mareo/terapia
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