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1.
Acta Psychol (Amst) ; 216: 103299, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33799104

RESUMO

Attention and working memory (WM) are under high genetic regulation. Single nucleotide polymorphisms (SNPs) of the CNR1 gene, that encode for CB1R, have previously been shown to be related with individual differences in attentional control and WM. However, it remains unclear whether there is an allele-dosage or a dominant contribution of polymorphisms of CNR1 affecting attention and WM performance. This study evaluated the associations between attention and WM performance and three SNPs of CNR1: rs1406977, rs2180619, and rs1049353, previously associated with both processes. Healthy volunteers (n = 127) were asked to perform the Attention Network Task (ANT) to evaluate their overall attention and alerting, orienting, and executive systems, and the n-back task for evaluating their WM. All subjects were genotyped using qPCR with TaqMan assays; and dominant and additive models were assessed using the risk alleles of each SNP as the predictor variable. Results showed an individual association of the three SNPs with attention performance, but the composite genotype by the three alleles had the greatest contribution. Moreover, the additive-dosage model showed that for each G-allele added to the genotypic configuration, there was an increase in the percentage of correct responses respect to carriers who have no risk alleles in their genotypic configuration. The number of risk alleles in the genotypic configurations did not predict efficiency in any of the attention systems, nor in WM performance. Our model showed a contribution of three single nucleotide polymorphisms of the CNR1 gene to explain 9% of the variance of attention in an additive manner.

2.
Biomedicines ; 9(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809387

RESUMO

Considering the high prevalence of cartilage-associated pathologies, low self-repair capacity and limitations of current repair techniques, tissue engineering (TE) strategies have emerged as a promising alternative in this field. Three-dimensional culture techniques have gained attention in recent years, showing their ability to provide the most biomimetic environment for the cells under culture conditions, enabling the cells to fabricate natural, 3D functional microtissues (MTs). In this sense, the aim of this study was to generate, characterize and compare scaffold-free human hyaline and elastic cartilage-derived MTs (HC-MTs and EC-MTs, respectively) under expansion (EM) and chondrogenic media (CM). MTs were generated by using agarose microchips and evaluated ex vivo for 28 days. The MTs generated were subjected to morphometric assessment and cell viability, metabolic activity and histological analyses. Results suggest that the use of CM improves the biomimicry of the MTs obtained in terms of morphology, viability and extracellular matrix (ECM) synthesis with respect to the use of EM. Moreover, the overall results indicate a faster and more sensitive response of the EC-derived cells to the use of CM as compared to HC chondrocytes. Finally, future preclinical in vivo studies are still needed to determine the potential clinical usefulness of these novel advanced therapy products.

3.
Vaccines (Basel) ; 9(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810023

RESUMO

BACKGROUND: The reemergence of measles represents a public health problem. The aim of the study was to determine the seroprevalence of IgG antibodies against measles in children of three ethnic groups in southern Mexico and the nutritional status and demographic risk factors associated. METHODS: A cross-sectional study in 416 school-age children, 207 belonging to the Tlapaneco ethnic group, 101 to the Mixteco group and 108 were considered Mestizo. Sociodemographic data were collected, an anthropometric evaluation of the children was performed and a fasting blood sample was obtained from each child for the measurement of measles IgG antibodies by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: From the total sample, 59% of the children were seropositive for IgG antibodies against measles; in contrast, 41% lacked IgG antibodies. Measles antibody seropositivity was higher in girls (64%). 90.5% of 6-year-old children had higher antibodies seroprevalence, compared to the children between 10 and 13 years old (45.5%). In the three ethnic groups, age was negatively correlated with the index standard ratio (ISR) of measles antibody levels and the families with ≥8 members showed less seropositivity. According to the antibodies levels, most of the positive cases remained around 1 Standard Deviation (SD) of the ISR values and no underweight children had antibody levels above 2 SD. CONCLUSIONS: The Anti-Measles serological coverage is low in children of three ethnic groups from Southern Mexico and the age, sex, malnutrition and family size are associated factors. Therefore, it is important to strengthen immunization campaigns, principally in vulnerable groups.

4.
Int J Mol Sci ; 22(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673602

RESUMO

In critical nerve gap repair, decellularized nerve allografts are considered a promising tissue engineering strategy that can provide superior regeneration results compared to nerve conduits. Decellularized nerves offer a well-conserved extracellular matrix component that has proven to play an important role in supporting axonal guiding and peripheral nerve regeneration. Up to now, the known decellularized techniques are time and effort consuming. The present study, performed on rat sciatic nerves, aims at investigating a novel nerve decellularization protocol able to combine an effective decellularization in short time with a good preservation of the extracellular matrix component. To do this, a decellularization protocol proven to be efficient for tendons (DN-P1) was compared with a decellularization protocol specifically developed for nerves (DN-P2). The outcomes of both the decellularization protocols were assessed by a series of in vitro evaluations, including qualitative and quantitative histological and immunohistochemical analyses, DNA quantification, SEM and TEM ultrastructural analyses, mechanical testing, and viability assay. The overall results showed that DN-P1 could provide promising results if tested in vivo, as the in vitro characterization demonstrated that DN-P1 conserved a better ultrastructure and ECM components compared to DN-P2. Most importantly, DN-P1 was shown to be highly biocompatible, supporting a greater number of viable metabolically active cells.

5.
Clin Res Cardiol ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687519

RESUMO

OBJECTIVES: The objective of our work is to evaluate the prognostic benefit of an early invasive strategy in patients with high-risk NSTACS according to the recommendations of the 2020 clinical practice guidelines during long-term follow-up. METHODS: This retrospective observational study included 6454 consecutive NSTEACS patients. We analyze the effects of early coronary angiography (< 24 h) in patients with: (a) GRACE risk score > 140 and (b) patients with "established NSTEMI" (non ST-segment elevation myocardial infarction defined by an increase in troponins) or dynamic ST-T-segment changes with a GRACE risk score < 140. RESULTS: From 2003 to 2017, 6454 patients with "new high-risk NSTEACS" were admitted, and 6031 (93.45%) of these underwent coronary angiography. After inverse probability of treatment weighting, the long-term cumulative probability of being free of all-cause mortality, cardiovascular mortality and MACE differed significantly due to an early coronary intervention in patients with NSTEACS and GRACE > 140 [HR 0.62 (IC 95% 0.57-0.67), HR 0.62 (IC 95% 0.56-0.68), HR 0.57 (IC 95% 0.53-0.61), respectively]. In patients with NSTEACS and GRACE < 140 with established NSTEMI or ST/T-segment changes, the benefit of the early invasive strategy is only observed in the reduction of MACE [HR 0.62 (IC 95% 0.56-0.68)], but not for total mortality [HR 0.96 (IC 95% 0.78-1.2)] and cardiovascular mortality [HR 0.96 (IC 95% 0.75-1.24)]. CONCLUSIONS: An early invasive management is associated with reduced all-cause mortality, cardiovascular mortality and MACE in NSTEACS with high GRACE risk score. However, this benefit is less evident in the subgroup of patients with a GRACE score < 140 with established NSTEMI or ST/T-segment changes.

6.
Mar Pollut Bull ; 164: 112102, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33561583

RESUMO

The purpose of this work was to use the deep-water chimaera Hydrolagus colliei to examine the bioaccumulation and availability of Hg and Se in its deep-water habitat; the Se:Hg molar ratio was calculated to establish baseline information of the species and its associated ecosystem. The organisms were collected from northern Gulf of California. Hg levels in muscle were higher than liver and the opposite pattern happened with Se concentrations. Female had total lengths and weights higher than male but there were not found differences between elements concentrations by sex. Hg in muscle was correlated with weight. Molar Se:Hg ratio in muscle was the lowest compared to the liver. It was hypothesized that Hg and Se uptake to H. colliei were by its feeding habits because is a dominant species component of the demersal ecosystem and that play and important functional role in the control of oceanic ecosystem structure and function.


Assuntos
Mercúrio , Selênio , Poluentes Químicos da Água , Animais , California , Ecossistema , Monitoramento Ambiental , Feminino , Masculino , Mercúrio/análise , Oceanos e Mares , Selênio/análise , Poluentes Químicos da Água/análise
7.
Adv Exp Med Biol ; 1297: 83-95, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537938

RESUMO

The sleep-wake cycle is a complex process that includes wake (W), non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Each phase is regulated by specialized brain structures that, by means of different neurotransmitters, maintain the constant expression of the sleep-wake cycle. Molecules like orexin, serotonin, noradrenaline, histamine, for waking; GABA, adenosine, prostaglandins, for NREM sleep and acetylcholine and glutamate for REM sleep, among other molecules are responsible for the expression and maintenance of each phase. When the endocannabinoid system was being described for the first time, almost three decades ago, oleamide's sleep promoting properties were highlighted. Nowadays, enough evidence has been cumulated to support the endocannabinoid system role in the sleep-wake cycle regulation. The endocannabinoids oleamide anandamide, and 2-arachidonylglycerol promote NREM and/or REM sleep via the CB1R, thereby making this system a target to treat sleep disorders, such as insomnia.


Assuntos
Canabinoides , Encéfalo , Eletroencefalografia , Neurotransmissores , Sono , Sono REM , Vigília
8.
Minerva Anestesiol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591141

RESUMO

BACKGROUND: Optimal control of acute postoperative pain and prevention of chronic persistent pain in total hip arthroplasty (THA) remain a challenge. The main hypothesis was that peripheral nerve blocks improve postoperative analgesia. METHODS: Immediate postoperative pain (24 hours) was evaluated every hour in 510 patients using a verbal rating 11-point scale for patient self-reporting of pain (VRS-11). All patients received subarachnoid anesthesia (SA) and were randomly allocated in six groups: SA with morphine 0.1 (SA0.1) or 0.2 mg (SA0.2), fascia iliaca compartment block with dexamethasone 4 mg + levobupivacaine 0.375% 20 (FICB20) or 30 mL (FICB30), lateral femoral cutaneous nerve block with levobupivacaine 0.25% 5 ml (LFCNB) and FICB20+LFCNB. Standardized analgesia included intravenous metamizole magnesium, dexketoprofen and rescue with paracetamol and morphine, and/or regional rescue (FICB, LFCNB, femoral and sciatic nerve blocks). RESULTS: 37.5% of patients had at least one episode of pain, 31.3% of them needed rescue analgesia while the remaining 6.2% did not request analgesia. There were no significant differences between the groups in paracetamol, morphine and rescue nerve blocks requirements. There was pain only in 5.4% of the total PACU pain records: 3.1% mild pain, 1.7% moderate pain and 0.6% severe pain. CONCLUSIONS: Combined with a multimodal analgesic approach, infra-inguinal FICB and LFCNB did not improve immediate postoperative analgesia for THA in our hospital. Other options and longer-term studies should be more extensively investigated to determine the role of peripheral blocks in postoperative pain treatment protocols.

9.
Circ Cardiovasc Interv ; 14(2): e009342, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33541099

RESUMO

BACKGROUND: Limited data are available regarding change in the nutritional status after transcatheter aortic valve replacement (TAVR). This study evaluated the prognostic impact of the change in the geriatric nutritional risk index following TAVR. METHODS: TAVR patients were analyzed in a prospective and observational study. To analyze the change in nutritional status, geriatric nutritional risk index of the patients was calculated on the day of TAVR and at 3-month follow-up. The impact of the change in nutritional risk index after TAVR on all-cause mortality, heart failure hospitalization (HF-h), and the composite of all-cause death and HF hospitalization was analyzed using the Cox Proportional Hazards model. RESULTS: Four hundred thirty-three patients were included. After TAVR, 68.4% (n=182) patients with baseline nutritional risk improved compared with 31.6% (n=84) who remained at nutritional risk. The change from no-nutritional risk to nutritional risk after TAVR occurred in 15.0% (n=25), while 85.0% (n=142) remained without risk of malnutrition. During follow-up, 157 (36.3%) patients died and 172 patients (39.7%) were hospitalized due to HF. Patients who continued to be at nutritional risk had a higher risk of mortality (hazard ratio [HR], 2.10 [95% CI, 1.30-3.39], P=0.002), HF-h (HR, 1.97 [95% CI, 1.26-3.06], P=0.000), and the composite of death and HF-h (HR, 2.0 [95% CI, 1.37-2.91], P<0.001). The change to non-nutritional risk after TAVR significantly impacted mortality (HR, 0.48 [95% CI, 0.30-0.78], P=0.003), HF-h (HR, 0.50 [95% CI, 0.34-0.74], P=0.001), and the composite outcome (HR, 0.44 [95% CI, 0.32-0.62], P<0.001). CONCLUSIONS: Remaining at nutritional risk after TAVR confers a poor prognosis and is associated with an increased risk of mortality and HF-h, while the change from risk of malnutrition to non-nutritional risk after TAVR was associated with a halving of the risk of mortality and HF-h. Further studies are needed to identify whether patients at nutritional risk would benefit from nutritional intervention during processes of care of TAVR programs.

10.
Soc Neurosci ; 16(2): 145-152, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33529536

RESUMO

Drug dependence is a debilitating disorder, affecting 30 million people worldwide. In this short review we discuss about the plasticity changes in the reward and defense brain systems induced by early-life psychosocial stressful experiences. Such changes may render persons more vulnerable to illicit drugs use, facilitating behaviors of abuse and development of addiction. We propose that underlying plasticity changes render brain reward system as increasingly fragile because of tolerance and other physiological effects that reduce responsiveness with repeated use. In contrast, we propose that brain defense system makes maintain antifragile mechanisms that generate more robust responses with the prolonged consumption of drugs. Investigating the underlying mechanisms of these brain plasticity changes may advance the development of more efficacious pharmacologic and psychotherapeutic approaches to rehabilitate patients and more efficacious prevention policies to protect children from stressful experiences.

11.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445493

RESUMO

Acellular nerve allografts (ANGs) represent a promising alternative in nerve repair. Our aim is to improve the structural and biomechanical properties of biocompatible Sondell (SD) and Roosens (RS) based ANGs using genipin (GP) as a crosslinker agent ex vivo. The impact of two concentrations of GP (0.10% and 0.25%) on Wistar rat sciatic nerve-derived ANGs was assessed at the histological, biomechanical, and biocompatibility levels. Histology confirmed the differences between SD and RS procedures, but not remarkable changes were induced by GP, which helped to preserve the nerve histological pattern. Tensile test revealed that GP enhanced the biomechanical properties of SD and RS ANGs, being the crosslinked RS ANGs more comparable to the native nerves used as control. The evaluation of the ANGs biocompatibility conducted with adipose-derived mesenchymal stem cells cultured within the ANGs confirmed a high degree of biocompatibility in all ANGs, especially in RS and RS-GP 0.10% ANGs. Finally, this study demonstrates that the use of GP could be an efficient alternative to improve the biomechanical properties of ANGs with a slight impact on the biocompatibility and histological pattern. For these reasons, we hypothesize that our novel crosslinked ANGs could be a suitable alternative for future in vivo preclinical studies.

12.
Nutr Neurosci ; : 1-13, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33269659

RESUMO

Some reports have described that a high fructose diet is associated with a deficit of hippocampus-dependent cognitive functions. In this study, we have evaluated the effects of fructose on spatial memory and molecular markers in the hippocampus and prefrontal cortex and analyzed whether those alterations are reversible. Male Wistar rats (n = 60) began their treatment during adolescence. A group was forced to drink a solution of 10% fructose for twelve weeks. Another group was subjected to the same fructose intake schedule, but later fructose was removed, and tap water was provided for four weeks. After treatments, spatial memory was evaluated with Barnes maze. Different neurogenesis, inflammation, astrocyte, and energy homeostasis markers were evaluated with immunofluorescence, ELISA, and Western blot. Changes were analyzed using two-way repeated-measures ANOVA, one-way ANOVA, and Tukeýs posthoc test (p < 0.05). Results showed that after long-term consumption of fructose, there was an impairment of spatial memory. This deficit was concomitant with the abolition of hippocampal neurogenesis and significant increases of IL-1b in the hippocampus and prefrontal cortex. Levels of COX-2 were decreased in the hippocampus. Besides, fructose induced a significant increase in GFAP and a decrease of glutamine synthetase. Likewise, energy homeostasis-associated neuropeptide orexin-A and their receptors (ORX R1 and ORX R2) were significantly increased. The spatial memory deficit, neuroinflammation, and changes in some proteins expression were permanent one month after the fructose elimination from the diet. These results suggest that fructose induces substantial hippocampal and cortical changes, and those are irreversible after a shift in the diet.

13.
J Nanobiotechnology ; 18(1): 174, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228673

RESUMO

BACKGROUND: Treatment of patients affected by severe burns is challenging, especially due to the high risk of Pseudomonas infection. In the present work, we have generated a novel model of bioartificial human dermis substitute by tissue engineering to treat infected wounds using fibrin-agarose biomaterials functionalized with nanostructured lipid carriers (NLCs) loaded with two anti-Pseudomonas antibiotics: sodium colistimethate (SCM) and amikacin (AMK). RESULTS: Results show that the novel tissue-like substitutes have strong antibacterial effect on Pseudomonas cultures, directly proportional to the NLC concentration. Free DNA quantification, WST-1 and Caspase 7 immunohistochemical assays in the functionalized dermis substitute demonstrated that neither cell viability nor cell proliferation were affected by functionalization in most study groups. Furthermore, immunohistochemistry for PCNA and KI67 and histochemistry for collagen and proteoglycans revealed that cells proliferated and were metabolically active in the functionalized tissue with no differences with controls. When functionalized tissues were biomechanically characterized, we found that NLCs were able to improve some of the major biomechanical properties of these artificial tissues, although this strongly depended on the type and concentration of NLCs. CONCLUSIONS: These results suggest that functionalization of fibrin-agarose human dermal substitutes with antibiotic-loaded NLCs is able to improve the antibacterial and biomechanical properties of these substitutes with no detectable side effects. This opens the door to future clinical use of functionalized tissues.

15.
Front Psychiatry ; 11: 558691, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192674

RESUMO

Introduction: Any viral pandemic is a global health and mental health issue. The World Health Organization and mental health associations have warned that the current COVID-19 pandemic will lead to a drastic increase of stress-related conditions and mental health issues globally. Materials and Methods: An online web-based survey has been launched from 10 to 15 April 2020 in Paraguay in order to collect information regarding the stress related to the quarantine during the COVID-19 pandemic. It has been spread through social media ("WhatsApp," "Twitter," and "Facebook"). Two thousand two hundred and six Paraguayan citizens, over 18 years of age, completed the survey voluntarily. Socio-demographics as well as ratings at Self-perceived Stress Scale have been collected and analyzed. Results: Two thousand two hundred and six subjects (74.12% men) aged between 18 and 75 with an average of 34 ± 11 years old completed the survey. 12.42% (276 subjects) of sample reported a preexisting diagnosis of mental disorder, and 175 participants (7.93%) reported an increase of preexisting symptoms with the onset of COVID-19 quarantine. 41.97% of them had anxiety and 54.38% did not receive any specific treatment. The general population rated 18.10 ± 5.99 at Self-perceived Stress Scale, which indicates a moderate level of self-perceived stress. Significant association was found between higher levels of stress and female sex, being single, or reporting preexisting mental disorder, above all anxiety and depression (p < 0.01). In fact, in 63.87% of mentally ill subjects (n = 175), the quarantine has worsened symptoms of preexisting mental disorders. Conclusion: This study suggests a stressful impact of COVID-19 pandemic, with the majority of participants reporting a moderate level of self-perceived stress. We suggest mental health services to provide a phone-based or web-based support to the general population in order to contrast the psychological impact of the pandemic. This approach may improve the accessibility to mental healthcare services in Paraguay, especially in times of social distancing.

16.
J Cosmet Dermatol ; 19(12): 3183-3188, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33098221

RESUMO

BACKGROUND: Delusional infestation is a primary psychiatric disorder characterized by a somatic-type delusional disorder (primary delusional infestation) that may lead to self-induced cutaneous lesions which are often difficult to recognize and treat properly. It may be also secondary to other psychiatric disorders, medical diseases, or substance abuse. AIMS: This review will describe prevalence, common clinical features, different clinical presentations, differential diagnoses, and treatment recommendation. Special focus has been put on psychological aspects. METHODS: We conducted a literature search on PubMed from January 2001 to June 2020 with the search terms of delusional parasitosis, delusional infestation, psychological, Reference lists of identified articles were examined for further relevant studies. The search was limited to English language articles. No specified quality criteria were used for study inclusion. RESULTS: The clinical manifestations of delusional infestation are very important in the differential diagnosis and its psychological implications and management perspectives. CONCLUSION: This article presents an update regarding the clinical aspects and treatment options of delusional infestation in order to provide an up-to-date review for dermatologists and general practitioners.

18.
Dermatol Ther ; : e13466, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015928

RESUMO

Hair-pulling disorder (Trichotillomania) is a disabling mental disorder. Patient's behavior is characterized by the recurrent pulling of own hair with hair loss and a marked dysfunction in various areas of daily life. Trichotillomania is a relatively common disorder with pediatric onset, often associated with significant morbidity, comorbidity, and functional decline. Surprisingly, children or adolescents have been little studied in the research studies on the pathophysiology and psychopathology of trichotillomania. Furthermore, more evidences regarding the effective and evidence-based pharmacological interventions for the treatment of this condition are encouraged. This narrative review will report on the etiopathogenesis and clinical manifestations of trichotillomania including criteria for diagnosis and treatment issues of this complex mental disorder.

19.
Biomolecules ; 10(11)2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33114390

RESUMO

Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the microbiota variability could modify the employment of direct and indirect mechanisms in the response to treatment. The main objective of this review was to understand the gut microbiota bacterial variability in patients with RA, pre and post-treatment with DMARDs, and to identify the possible mechanisms through which microbiota can regulate the response to pharmacological therapy.

20.
Sci Transl Med ; 12(567)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115953

RESUMO

Meniscus tears are common knee injuries and a major osteoarthritis (OA) risk factor. Knowledge gaps that limit the development of therapies for meniscus injury and degeneration concern transcription factors that control the meniscus cell phenotype. Analysis of RNA sequencing data from 37 human tissues in the Genotype-Tissue Expression database and RNA sequencing data from meniscus and articular cartilage showed that transcription factor Mohawk (MKX) is highly enriched in meniscus. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). In mesenchymal stem cells (MSCs), the combination of adenoviral MKX (Ad-MKX) and transforming growth factor-ß3 (TGF-ß3) induced a meniscus cell phenotype. When Ad-MKX-transduced MSCs were seeded on TGF-ß3-conjugated decellularized meniscus scaffold (DMS) and inserted into experimental tears in meniscus explants, they increased glycosaminoglycan content, extracellular matrix interconnectivity, cell infiltration into the DMS, and improved biomechanical properties. Ad-MKX injection into mouse knee joints with experimental OA induced by surgical destabilization of the meniscus suppressed meniscus and cartilage damage, reducing OA severity. Ad-MKX injection into human OA meniscus tissue explants corrected pathogenic gene expression. These results identify MKX as a previously unidentified key transcription factor that regulates the meniscus cell phenotype. The combination of Ad-MKX with TGF-ß3 is effective for differentiation of MSCs to a meniscus cell phenotype and useful for meniscus repair. MKX is a promising therapeutic target for meniscus tissue engineering, repair, and prevention of OA.

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