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1.
PLoS Genet ; 17(6): e1009534, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34086673

RESUMEN

Assumptions are made about the genetic model of single nucleotide polymorphisms (SNPs) when choosing a traditional genetic encoding: additive, dominant, and recessive. Furthermore, SNPs across the genome are unlikely to demonstrate identical genetic models. However, running SNP-SNP interaction analyses with every combination of encodings raises the multiple testing burden. Here, we present a novel and flexible encoding for genetic interactions, the elastic data-driven genetic encoding (EDGE), in which SNPs are assigned a heterozygous value based on the genetic model they demonstrate in a dataset prior to interaction testing. We assessed the power of EDGE to detect genetic interactions using 29 combinations of simulated genetic models and found it outperformed the traditional encoding methods across 10%, 30%, and 50% minor allele frequencies (MAFs). Further, EDGE maintained a low false-positive rate, while additive and dominant encodings demonstrated inflation. We evaluated EDGE and the traditional encodings with genetic data from the Electronic Medical Records and Genomics (eMERGE) Network for five phenotypes: age-related macular degeneration (AMD), age-related cataract, glaucoma, type 2 diabetes (T2D), and resistant hypertension. A multi-encoding genome-wide association study (GWAS) for each phenotype was performed using the traditional encodings, and the top results of the multi-encoding GWAS were considered for SNP-SNP interaction using the traditional encodings and EDGE. EDGE identified a novel SNP-SNP interaction for age-related cataract that no other method identified: rs7787286 (MAF: 0.041; intergenic region of chromosome 7)-rs4695885 (MAF: 0.34; intergenic region of chromosome 4) with a Bonferroni LRT p of 0.018. A SNP-SNP interaction was found in data from the UK Biobank within 25 kb of these SNPs using the recessive encoding: rs60374751 (MAF: 0.030) and rs6843594 (MAF: 0.34) (Bonferroni LRT p: 0.026). We recommend using EDGE to flexibly detect interactions between SNPs exhibiting diverse action.


Asunto(s)
Modelos Genéticos , Catarata/genética , Conjuntos de Datos como Asunto , Diabetes Mellitus Tipo 2/genética , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Glaucoma/genética , Humanos , Hipertensión/genética , Degeneración Macular/genética , Fenotipo , Polimorfismo de Nucleótido Simple
2.
J Med Virol ; 95(12): e29305, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38116715

RESUMEN

The use of adeno-associated virus (AAV) vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion-associated reactions (IARs) pose a significant challenge to the safety and efficacy of AAV-based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll-like receptor activation and subsequent production of pro-inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies (Nabs) and T-cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre-existing Nabs, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu-like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre- and postadministration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV-based gene therapy.


Asunto(s)
Dependovirus , Vectores Genéticos , Humanos , Dependovirus/genética , Terapia Genética , Anticuerpos Neutralizantes , Linfocitos T
3.
J Biomed Inform ; 129: 104054, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35331966

RESUMEN

Vaccination is the most effective way to provide long-lasting immunity against viral infection; thus, rapid assessment of vaccine acceptance is a pressing challenge for health authorities. Prior studies have applied survey techniques to investigate vaccine acceptance, but these may be slow and expensive. This study investigates 29 million vaccine-related tweets from August 8, 2020 to April 19, 2021 and proposes a social media-based approach that derives a vaccine acceptance index (VAI) to quantify Twitter users' opinions on COVID-19 vaccination. This index is calculated based on opinion classifications identified with the aid of natural language processing techniques and provides a quantitative metric to indicate the level of vaccine acceptance across different geographic scales in the U.S. The VAI is easily calculated from the number of positive and negative Tweets posted by a specific users and groups of users, it can be compiled for regions such a counties or states to provide geospatial information, and it can be tracked over time to assess changes in vaccine acceptance as related to trends in the media and politics. At the national level, it showed that the VAI moved from negative to positive in 2020 and maintained steady after January 2021. Through exploratory analysis of state- and county-level data, reliable assessments of VAI against subsequent vaccination rates could be made for counties with at least 30 users. The paper discusses information characteristics that enable consistent estimation of VAI. The findings support the use of social media to understand opinions and to offer a timely and cost-effective way to assess vaccine acceptance.


Asunto(s)
COVID-19 , Medios de Comunicación Sociales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Procesamiento de Lenguaje Natural , Vacunación
4.
Plant Cell Rep ; 41(4): 1025-1041, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35099611

RESUMEN

KEY MESSAGE: The overexpression of HaCYC2c and its regulation on HaNDUA2 through transcriptional recognition are important for regulating the heteromorphous development and functional differentiation of ray and disc florets in sunflower. Flower symmetry is closely related to pollinator recruitment and individual fecundity for higher plants and is the main feature used to identify flower type in angiosperms. In sunflower, HaCYC2c regulates floral organ development and floral symmetry, but the specific detail remains unclear. In this study, sunflower long petal mutant (lpm) with HaCYC2c insertion mutation was used to investigate the regulating role of HaCYC2c in the morphogenesis of florets and the transformation of floral symmetry through phenotype, transcriptome, qRT-PCR, and possible protein-gene interactions analyses. Results showed that HaCYC2c was overexpressed after an insertion into the promoter region. This gene could recognize the cis-acting element GGTCCC in the promoter region of HaNDUA2 that might regulate HaNDUA2 and affect other related genes. As a consequence, the abnormal elongation of disc petals and the degradation of male reproductive system occurred at the early development of floral organ in sunflower. Furthermore, this insertion mutation resulted in floral symmetry transformation, from actinomorphy to zygomorphy, thereby making the tubular disc florets transformed into ray-like disc florets in sunflower lpm. The findings suggested that the overexpression of HaCYC2c and its control of HaNDUA2 through transcriptional recognition might be an important regulating node of the heteromorphous development and functional differentiation for ray and disc florets in sunflower. This node contributes to the understanding of the balance between pollinator recruitment capacity of ray florets and fertility of disc florets for the optimization of reproductive efficiency and enhancement of species competitiveness in sunflower.


Asunto(s)
Asteraceae , Helianthus , Flores/genética , Regulación de la Expresión Génica de las Plantas , Helianthus/genética , Fenotipo
5.
J Musculoskelet Neuronal Interact ; 22(1): 132-141, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35234168

RESUMEN

OBJECTIVE: To explore the role and mechanism of chondrogenic bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on Rheumatoid arthritis (RA). METHODS: The chondrogenesis of BMSCs was induced by chondrogenic medium. Exosomes from BMSCs and chondrogenic BMSCs were isolated and characterized by transmission electron microscope (TEM), laser particle size analyzer and western blot. ELISA was used to analyze the expression levels of pro-inflammatory cytokines and matrix metalloproteinases (MMPs). Western bolt was performed to assess MAPK and NF-κB pathways expression. The inflammation score and the pathological damage of RA mice were evaluated. Luciferase reporter assay and RIP were carried out to examine the relationship between microRNA-205-5p (miR-205-5p) and mouse double minute 2 (MDM2). RESULTS: Chondrogenic BMSCs-derived exosomes suppressed pro-inflammatory cytokines, MMPs and MAPK and NF-κB pathways in RA-FLSs. miR-205-5p had a high expression in chondrogenic BMSCs-derived exosomes. Functionally, exosomal miR-205-5p also played the anti-inflammation effects. Besides, MDM2 was a direct target of miR-205-5p. Additionally, chondrogenic BMSCs-secreted exosomal miR-205-5p suppressed the inflammation score, joint destruction, and inflammatory response in collagen-induced arthritis (CIA) mice through MDM2. CONCLUSION: Chondrogenic BMSCs-derived exosomal miR-205-5p suppressed inflammatory response, MAPK and NF-κB pathways through MDM2 in RA, indicating exosomal miR-205-5p might be a potential target for RA treatment.


Asunto(s)
Artritis Reumatoide , Exosomas , Células Madre Mesenquimatosas , MicroARNs , Proteínas Proto-Oncogénicas c-mdm2 , Sinoviocitos , Animales , Artritis Reumatoide/patología , Condrogénesis , Citocinas/metabolismo , Exosomas/metabolismo , Exosomas/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Inflamación/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , MicroARNs/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Sinoviocitos/metabolismo , Sinoviocitos/patología
6.
Trop Anim Health Prod ; 53(3): 344, 2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34091758

RESUMEN

So far, few animals with the ability of lignin degradation have been reported except termite and longicorn. In this study, it was found that the crude fiber and acid detergent lignin (ADL) of rice straw can be degraded dramatically higher by buffalo than those by cattle. In order to further study this ability of buffalo, the digestion of roughages in buffalo rumen was studied using rumen nylon bag experiment, scanning electron microscopy (SEM), and Van Soest fiber analysis. The SEM results showed that the degradation degree of rice straw was dramatically higher in buffalo than that in cattle. The digestibility of crude fiber was significantly higher in buffalo than that in cattle (P < 0.01). The digestibility of ADL, cellulose, hemicellulose, acid detergent, fiber, and neutral detergent fiber of rice straw in buffalo rumen was significantly higher than that in cattle (P < 0.05). The ADL degradation rate of rice straw in buffalo rumen was significantly higher than that in cattle rumen, indicating that buffalo was capable of utilizing lignin and had superior utilizing capability than cattle. It was observed that various roughages can be dramatically digested by buffalo rumen with the ranking of ADL degradation rate: peanut vine (15.04%) > rice silage > maize silage > rice straw > corn stover > wheat stalk > bract leaf > potato vine (7.22%), verifying that buffalo rumen possessed the ability to digest universal roughages. In conclusion, this study revealed that buffalo was more efficient in ADL degradation compared with cattle.


Asunto(s)
Búfalos , Lignina , Alimentación Animal/análisis , Animales , Bovinos , Fibras de la Dieta/metabolismo , Digestión , Fermentación , Lignina/metabolismo , Rumen/metabolismo , Ensilaje/análisis , Zea mays
7.
Med Sci Monit ; 25: 3558-3565, 2019 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-31086125

RESUMEN

BACKGROUND Type 2 diabetes mellitus (T2DM) is related to the serum carcinoembryonic antigen (CEA) level, which is used as a marker of colorectal cancer. Obstructive sleep apnea-hypopnea syndrome (OSAS) has been recently reported to have cancer-promoting effects. The aim of our study was to observe the effect of OSAS on serum levels of CEA in patients with T2DM. MATERIAL AND METHODS We enrolled 401 T2DM patients in this study. There were 244 patients with OSAS and 157 patients without OSAS. RESULTS The CEA level in T2DM patients with OSAS was higher than that in those without OSAS (p<0.05). The participants with AHI scores ≥30 had higher CEA levels than those with 5≤ AHI scores <30 (p<0.05). The AHI score and ODI score were independently associated with increased risk of high CEA level in T2DM patients (odds ratio [OR]=1.052, 95% confidence interval [CI]: 1.011~1.095) and (OR=1.214, 95% CI: 1.070~1.377). Moreover, among male T2DM patients, the AHI score and ODI score had a linear correlation with the CEA level; this association was also observed in T2DM patients who smoked, had an HbA1c level ≥7%, or had a BMI ≥28 kg/m2 (all p<0.05). CONCLUSIONS The AHI score and ODI score were positively associated with the CEA level in T2DM patients. The relationship was stronger in male T2DM patients and in those who smoked, were obese, or had poor glycemic control. The mechanism may be related to metabolic disorders, and the potential increased risk of colorectal cancer should be investigated in a prospective study.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Síndromes de la Apnea del Sueño/metabolismo , Apnea Obstructiva del Sueño/metabolismo , Adulto , Índice de Masa Corporal , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/sangre , Enfermedades Cardiovasculares/complicaciones , China , Femenino , Humanos , Hiperglucemia/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Polisomnografía , Síndromes de la Apnea del Sueño/sangre , Apnea Obstructiva del Sueño/sangre
8.
PeerJ ; 12: e16831, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38464756

RESUMEN

In the context of global climate change, drought and soil salinity are some of the most devastating abiotic stresses affecting agriculture today. PYL proteins are essential components of abscisic acid (ABA) signaling and play critical roles in responding to abiotic stressors, including drought and salt stress. Although PYL genes have been studied in many species, their roles in responding to abiotic stress are still unclear in the sunflower. In this study, 19 HaPYL genes, distributed on 15 of 17 chromosomes, were identified in the sunflower. Fragment duplication is the main cause of the expansion of PYL genes in the sunflower genome. Based on phylogenetic analysis, HaPYL genes were divided into three subfamilies. Members in the same subfamily share similar protein motifs and gene exon-intron structures, except for the second subfamily. Tissue expression patterns suggested that HaPYLs serve different functions when responding to developmental and environmental signals in the sunflower. Exogenous ABA treatment showed that most HaPYLs respond to an increase in the ABA level. Among these HaPYLs, HaPYL2a, HaPYL4d, HaPYL4g, HaPYL8a, HaPYL8b, HaPYL8c, HaPYL9b, and HaPYL9c were up-regulated with PEG6000 treatment and NaCl treatment. This indicates that they may play a role in resisting drought and salt stress in the sunflower by mediating ABA signaling. Our findings provide some clues to further explore the functions of PYL genes in the sunflower, especially with regards to drought and salt stress resistance.


Asunto(s)
Helianthus , Helianthus/genética , Ácido Abscísico/farmacología , Proteínas de Plantas/genética , Sequías , Filogenia , Estrés Salino
9.
Int J Infect Dis ; 146: 107105, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38782355

RESUMEN

People with long COVID are those who still have symptoms, signs, and conditions after the initial phase of infection of SARS-CoV-2. The incidence of long COVID varies among regions-31% in North America, 44% in Europe, and 51% in Asia, which is challenging the healthcare system, but there is limited guidelines for its treatment. With more and more nationwide projects funded by the government such as the RECOVER initiative in the United States and National Institute for Health Research funding in the United Kingdom, an increasing number of ongoing clinical trials are investigating the efficacy of diverse therapies on reversing long COVID. After searching the World Health Organization International Clinical Trial Registry Platform, 587 clinical studies are identified as long COVID studies. Among these, 312 studies (53.2%) are testing potential therapies. Most of the long COVID trials were conducted in the United States (58 trials [18.6%]), followed by India (55 trials [17.6%]), and Spain (20 trials [6.4%]). Interventions in these clinical trials include physical exercise, rehabilitation therapy, behavioral therapy, and pharmacological therapies including herbs, paxlovid, and fluvoxamine. These trials are aiming to deal with these long COVID symptoms and signs including fatigue, decreased pulmonary function, reduced cognitive function, and others. To date, only 11 of these 312 studies have published their results that were not confirmative, unfortunately. Future studies should be designed to address sleep disorders which were seldomly included in registered clinical studies. Moreover, interventions aimed at treating the underlying pathophysiology of long COVID are also necessary but currently lacking.

10.
PLoS One ; 18(12): e0295255, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38039302

RESUMEN

The objective of this study was to investigate the direct effects of pain-induced depression and anxiety, as well as the mediating role of psychological resilience, on the psychological distress associated with rheumatoid arthritis. The method involved a sample of 196 patients with rheumatoid arthritis and applied the Hospital Anxiety and Depression Scale, Connor-Davidson Resilience Scale, and visual analog scale for pain. Bivariate and path analyses were performed, and a multiple mediational model was utilized. Results showed that all correlations among study variables were significant (p < 0.01). A partial mediation effect of psychological resilience was observed, and direct effects among the variables (pain, psychological resilience, anxiety, and depression) were statistically significant, including the direct effect of psychological resilience on depression and anxiety. The indirect effects of pain through psychological resilience on depression and anxiety were also significant. Thus, the results suggest that psychological resilience partially mediates the effects of pain-induced anxiety and depression in patients with rheumatoid arthritis.


Asunto(s)
Artritis Reumatoide , Resiliencia Psicológica , Humanos , Estudios Transversales , Depresión/psicología , Ansiedad/psicología , Artritis Reumatoide/complicaciones , Dolor
11.
Artículo en Inglés | MEDLINE | ID: mdl-37416532

RESUMEN

The high levels of bile acids are a critical factor in hepatorenal syndrome. Organic solute transporter α/ß (Ostα/ß) participate in bile acids reabsorption in the kidney. Fucoidan has the great potential in protecting against liver and kidney injury. However, whether Ostα/ß increase bile acids reabsorption in bile duct ligature (BDL)-induced hepatorenal syndrome and the blockade of fucoidan are still not clear. Male mice that received BDL were given to fucoidan (at 12.5, 25 and 50 â€‹mg/kg) through intraperitoneal injection once daily for three weeks. The serum, liver and kidney samples of these experimental mice were collected to carry out biochemical, pathological and Western blot analysis. In this study, fucoidan significantly lowered serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased serum levels of uric acid, creatinine and uric nitrogen, restored the deregulation of the renal urate transporter 1 (URAT1), organic anion transporter 1 (OAT1), and organic cation/carnitine transporter 1/2 (OCTN1/2), consistence with alleviation BDL-induced liver and kidney dysfunction, inflammation and fibrosis in mice. Furthermore, fucoidan significantly hampered Ostα/ß and reduced bile acids reabsorption in BDL-induced mice, protected against AML12 and HK-2 â€‹cells injury in vitro. These results demonstrate that fucoidan alleviates BDL-induced hepatorenal syndrome through inhibition Ostα/ß to reduce bile acids reabsorption in mice. Therefore, suppression of Ostα/ß by fucoidan may be a novel strategy for attenuating hepatorenal syndrome.

12.
Front Microbiol ; 14: 1103652, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37143543

RESUMEN

This study aimed to isolate and identify a ligninolytic bacterium from the rumen of buffalo (Bubalus bubalis) and investigate its effects as a silage additive for whole-plant rape. Three lignin-degradation strains were isolated from the buffalo rumen, with AH7-7 being chosen for further experiments. Strain AH7-7, with acid tolerance and a 51.4% survival rate at pH 4, was identified as Bacillus cereus. It exhibited a lignin-degradation rate of 20.5% after being inoculated in a lignin-degrading medium for 8 days. We divided the rape into four groups according to the various additive compositions to examine the fermentation quality, nutritional value, and bacterial community after ensiling: Bc group (inoculated with B. cereus AH7-7 3.0 × 106 CFU g FW-1), Blac group (inoculated with B. cereus AH7-7 1.0 × 106 CFU g FW-1, L. plantarum 1.0 × 106 CFU g FW-1, and L. buchneri 1.0 × 106 CFU g FW-1), Lac group (inoculated with L. plantarum 1.5 × 106 CFU g FW-1 and L. buchneri 1.5 × 106 CFU g FW-1), and Ctrl group (no additives). After 60 days of fermentation, the application of B. cereus AH7-7 was potent in modulating the fermentation quality of silage, especially when combined with L. plantarum and L. buchneri, as indicated by lower dry matter loss and higher contents of crude protein, water-soluble carbohydrate, and lactic acid. Furthermore, treatments with the B. cereus AH7-7 additive decreased the contents of acid detergent lignin, cellulose, and hemicellulose. The B. cereus AH7-7 additive treatments reduced the bacterial diversity and optimized the bacterial community compositions of silage, with an increase in the relative abundance of beneficial Lactobacillus and a decrease in the relative abundance of undesirable Pantoea and Erwinia. Functional prediction revealed that inoculation with B. cereus AH7-7 could increase the cofactors and vitamins metabolism, amino acid metabolism, translation, replication and repair, and nucleotide metabolism, while decreasing the carbohydrate metabolism, membrane transport, and energy metabolism. In brief, B. cereus AH7-7 improved the microbial community, fermentation activity, and ultimately the quality of silage. The ensiling with B. cereus AH7-7, L. plantarum, and L. buchneri combination is an effective and practical strategy to improve the fermentation and nutrition preservation of rape silage.

13.
Sci Total Environ ; 897: 165432, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37437629

RESUMEN

Nanoplastics (NPs) have emerged as a novel environmental threat due to their potential impacts on both animals and plants. Currently, research on the ecotoxicity of NPs has mainly focused on marine aquatic organisms and freshwater algae, with very limited investigations conducted on horticultural plants. This study examined the effects of varying concentrations (0, 1, 10, 50 mg·L-1) of polystyrene NPs (PS-NPs) on strawberry growth. The findings revealed that low concentrations of PS-NPs stimulated strawberry growth, whereas high concentrations impeded it. Notably, diverse strawberry cultivars displayed considerable differences in their sensitivity to PS-NP exposure. Laser scanning confocal microscopy confirmed the absorption of PS-NPs by strawberry roots, with variations in PS-NP accumulation observed across different cultivars. Comparative transcriptomics analysis suggested that the differential expression of genes responsible for calcium ion transport played a significant role in the observed intervarietal differences in PS-NP accumulation among strawberry cultivars. Furthermore, distinct variations in endogenous oxidative responses were observed in different strawberry cultivars under PS-NP treatment. Further analysis indicated that the down-regulation of peroxidase (POD) gene expression and terpenoid compounds accumulation were responsible for heightened endogenous oxidative stress observed in certain strawberry cultivars under PS-NP treatment. Transcriptomic and metabolomic analyses were performed on six strawberry cultivars to investigate their response to PS-NPs in terms of endogenous gene expression and metabolite accumulation. The results identified one commonly up-regulated gene (wall-associated receptor kinase-like) and sixteen commonly down-regulated genes associated with lipid metabolism and carbohydrate metabolism. In addition, a significant reduction in fatty acid metabolite accumulation was observed in the six strawberry cultivars under PS-NP treatment. These findings have significant implications for understanding the effects of NPs on strawberry growth, metabolism, and antioxidant responses, as well as identifying marker genes for monitoring and evaluating the impact of NP pollution on strawberry.


Asunto(s)
Fragaria , Animales , Microplásticos/metabolismo , Estrés Oxidativo , Fenotipo , Transcriptoma , Poliestirenos/toxicidad
14.
Front Med (Lausanne) ; 10: 1215858, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37654653

RESUMEN

Introduction: Chronic musculoskeletal pain bothers the quality of life for approximately 1.71 billion people worldwide. Although pharmacological therapies play an important role in controlling chronic pain, overuse of opioids, persistent or recurrent symptoms, and pain-related disability burden still need to be addressed. Heat-stone massage is using the heated stone to stimulate muscles and ligaments followed by massage for relax, which can potentially treat the chronic musculoskeletal pain. To determine the efficacy and safety of heat-stone massage for patients with chronic musculoskeletal pain is needed. Methods and analysis: This multicenter, 2-arm, randomized, positive drug-controlled trial will include a total of 120 patients with chronic musculoskeletal pain. The intervention group will receive a 2 week heat-stone massage, 3 times per week, whereas the control group will receive the flurbiprofen plaster twice per day for 2 weeks. The primary end point is the change in Global Pain Scale from baseline to the end of the 2 week intervention. The secondary outcomes include the pain severity (Numerical Rating Scale), pain acceptance (Chronic Pain Acceptance Questionnaire), self-management (Health Education Impact Questionnaire), self-efficacy (Pain Self-Efficacy Questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (Short Form-36). The intention-to-treat dataset will be used for analysis. Discussion: The pain management remains the research topic that patients always pay close attention to. This will be the first randomized clinical trial to evaluate whether heat-stone massage, a non-pharmacological therapy, is effective in the chronic musculoskeletal pain management. The results will provide evidence for new option of daily practice. Clinical trial registration: World Health Organization Chinese Clinical Trial Registry [ChiCTR2200065654; https://www.chictr.org.cn/showproj.html?proj=185403]; International Traditional Medicine Clinical Trial Registry [ITMCTR2022000104; http://itmctr.ccebtcm.org.cn/en-US/Home/ProjectView?pid=51776b6f-77b8-4811-9b5a-a0fec10f2cee].

15.
Cell Rep ; 42(7): 112794, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37459233

RESUMEN

Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ12-PGJ2, and 15d-PGJ2, which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic analysis of GPR44-/- LICs indicated that GPR44 activation by CyPGs suppressed KRAS-mediated MAPK and PI3K/AKT/mTOR signaling pathways, to enhance apoptosis. Our studies show the role of GPR44, providing mechanistic underpinnings of the chemopreventive and chemotherapeutic properties of selenium and CyPGs in AML.


Asunto(s)
Leucemia Mieloide Aguda , Selenio , Humanos , Ratones , Animales , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Línea Celular
16.
medRxiv ; 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37961706

RESUMEN

Mammalian cardiac muscle is supplied with blood by right and left coronary arteries that form branches covering both ventricles of the heart. Whether branches of the right or left coronary arteries wrap around to the inferior side of the left ventricle is variable in humans and termed right or left dominance. Coronary dominance is likely a heritable trait, but its genetic architecture has never been explored. Here, we present the first large-scale multi-ancestry genome-wide association study of dominance in 61,043 participants of the VA Million Veteran Program, including over 10,300 Africans and 4,400 Admixed Americans. Dominance was moderately heritable with ten loci reaching genome wide significance. The most significant mapped to the chemokine CXCL12 in both Europeans and Africans. Whole-organ imaging of human fetal hearts revealed that dominance is established during development in locations where CXCL12 is expressed. In mice, dominance involved the septal coronary artery, and its patterning was altered with Cxcl12 deficiency. Finally, we linked human dominance patterns with coronary artery disease through colocalization, genome-wide genetic correlation and Mendelian Randomization analyses. Together, our data supports CXCL12 as a primary determinant of coronary artery dominance in humans of diverse backgrounds and suggests that developmental patterning of arteries may influence one's susceptibility to ischemic heart disease.

17.
Genes (Basel) ; 13(5)2022 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-35627226

RESUMEN

The buffalo is an amazing ruminant. Its ability to degrade lignin, which has been recently reported, is most likely due to unique rumen microorganisms with lignin-degradation potential. Our goal was to explore the lignin-degradation potential of ruminal microorganisms, in which ligninolytic enzyme encoding genes were involved to provide ideas for revealing the mechanism of lignin degradation by buffalo. In this study, a bacterium strain identified as Bacillus cereus AH7-7 was isolated from the buffalo (Bubalus bubalis) rumen. After whole-genome sequencing, the results demonstrated that B. cereus AH7-7 had laccase, cytochrome P450 and vanillin alcohol oxidase-encoding genes. Sixty-four genes of B. cereus AH7-7 were involved in multiple aromatic metabolic pathways, such as phenylalanine metabolism and aminobenzoate degradation. A positive reaction resulting in guaiacol medium indicated that laccase secretion from B. cereus AH7-7 increased with time. A biodegradation experiment revealed that a significant reduction in kraft lignin content (25.9%) by B. cereus AH7-7 occurred at the end of 6 days of incubation, which confirmed its lignin-degradation capacity. Overall, this is the first report showing that B. cereus AH7-7 from the buffalo rumen can degrade lignin, and revealing the encoding genes of lignin-degrading enzymes from genome level.


Asunto(s)
Búfalos , Lignina , Animales , Bacillus cereus/genética , Bacillus cereus/metabolismo , Búfalos/genética , Búfalos/metabolismo , Lacasa/metabolismo , Lignina/metabolismo , Rumen/metabolismo
18.
Front Vet Sci ; 9: 935634, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36268048

RESUMEN

The present study aims to evaluate the effects of prepartum maternal supplementation of Capsicum oleoresin (CAP) on colostrum quality and growth performance in newborn buffalo calves. Twelve multiparous buffaloes were randomly assigned to two groups starting from 4 weeks prepartum: the control group with a basal diet (CON) and the treatment group with a basal diet supplemented with 20 mg CAP/kg dry matter (CAP20). After birth, all calves were weighed and received colostrum from their respective dam directly within 2 h. After that, calves received pasteurized milk and starter feed till 56 days of age. The results showed that CAP increased lactose (P < 0.05) in colostrum, and it tended to increase monounsaturated fatty acids; however, it decreased colostrum urea nitrogen (P < 0.10). CAP did not affect colostrum yield and immunoglobulin G and M concentrations. The weekly starter intake was not affected by maternal CAP supplementation during the first 6 weeks of life. There was an increasing tendency in weekly starter intake from weeks 7 and 8 (P < 0.10) in CAP20 compared with CON. At 7 days of age, calves in CAP20 had higher immunoglobulin G (P < 0.05) and a decreased tendency in calves' serum glucose compared with CON. Additionally, maternal CAP supplementation increased calves' serum ß-hydroxybutyric acid (P < 0.05) and tended to increase total protein (P < 0.10), while decreased non-esterified fatty acids (P < 0.05) at 56 days of age. Calves in CAP20 had higher final withers height, final heart girth, average withers height, and average heart girth than the CON (P < 0.05). These results suggest that maternal CAP supplementation could improve colostrum quality and positively affect the performance of buffalo calves.

19.
Front Microbiol ; 13: 1080650, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36620065

RESUMEN

Introduction: The rapid development of the farming industry has increased the amount of manure produced by livestock and poultry, causing increasingly prominent environmental pollution problems. In recent years, due to the increase in conventional bedding material costs, an increasing number of farmers choose to use harmless recycled manure as bedding. Manure bedding treatment of farms can not only solve the problem of manure pollution, but also resource utilization of manure and cost savings. Methods: This study compared the effects of five microbial agents (Microbial agents A, B, C, E, F) on buffalo manure bedding treatment by testing the temperature, moisture content, pH, microbial bacteria distribution of buffalo manure ectopic fermentation, and screened the lowest cost and most effective agent. The changes of microbial bacteria distribution in different periods of bedding treatment were also detected. Results: Agent A was eliminated because of poor fermentation effect and low fermentation temperature, which could not achieve the effect of harmless treatment. The other four agents of bacteria achieved a harmless effect, but the bedding treatment effect of agent F was significantly better than agent E, B, and C. In terms of the cost of agents: the cost of agent F required for fermenting 100m³ buffalo manure was the lowest, 1000yuan, followed by E (1200yuan), C (1750yuan), and B (1980yuan). In the process of ectopic fermentation bedding treatment of buffalo manure, Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Chloroflexi were the major bacteria used. The process was divided into three periods; the heating period - high temperature period - cooling period, the high temperature period could reach more than 75°C, and a large number of pathogenic bacteria and harmful bacteria, and other miscellaneous bacteria in the pile were degraded, their species diversity was reduced, and the structure of bacterial flora had significant differences in different treatment periods. In conclusion, this study has provided a guide for the resource utilization of manure in cattle farms and the reduction of manure pollution to the environment.

20.
Front Microbiol ; 13: 860694, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35495690

RESUMEN

Leaf anthracnose (LA) and anthracnose crown rot (ACR) represent serious fungal diseases that pose significant threats to strawberry production. To characterize the pathogen diversity associated with above diseases, 100 strawberry plants, including varieties of "Hongjia," "Zhangji," and "Tianxianzui," were sampled from Jiande and Zhoushan, the primary plantation regions of Zhejiang province, China. A total of 309 Colletotrichum isolates were isolated from crown (150 isolates) and leaves (159 isolates) of affected samples. Among these, 100 isolates obtained from the plants showing both LA and CR symptoms were selected randomly for further characterization. Based on the morphological observations combined with phylogenetic analysis of multiple genes (ACT, ITS, CAL, GAPDH, and CHS), all the 100 tested isolates were identified as C. gloeosporioides species complex, including 91 isolates of C. siamense, 8 isolates of C. fructicola causing both LA and ACR, and one isolate of C. aenigma causing ACR. The phenotypic characteristics of these isolated species were investigated using the BIOLOG phenotype MicroArray (PM) and a total of 950 different metabolic phenotype were tested, showing the characteristics among these isolates and providing the theoretical basis for pathogenic biochemistry and metabolism. The pathogenicity tests showed that even the same Colletotrichum species isolated from different diseased tissues (leaves or crowns) had significantly different pathogenicity toward strawberry leaves and crown. C. siamense isolated from diseased leaves (CSLA) was more aggressive than C. siamense isolated from rotted crown (CSCR) during the infection on "Zhangji" leaves. Additionally, C. fructicola isolated from affected leaf (CFLA) caused more severe symptoms on the leaves of four strawberry varieties compared to C. fructicola isolated from diseased crown (CFCR). For crown rot, the pathogenicity of CSCR was higher than that of CSLA.

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