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1.
Genomics ; 116(1): 110779, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38168627

RESUMO

Meat quality is a critical aspect of pig breeding. In addition to genetics, meat quality is also influenced by nutritional and environmental factors. In this study, three pig breeds, Shengxianhua, Jiaxing, and Qinglian Black (SXH, JXB and QLB), were used as experimental animals. Transcriptional analysis was performed on the longissimus thoracis (LT) muscle to investigate variations in intramuscular fat (IMF), inosine monophosphate (IMP), amino acids, and muscle fiber morphology across different breeds. Ingenuity canonical pathway analysis (IPA) identified biological processes and key driver genes related to metabolism and muscle development. Additionally, weighted gene co-expression network analysis (WGCNA) revealed gene modules associated with IMP. KEGG and GO analyses identified specific biological processes and signaling pathways related to IMP, including the Oxidative Phosphorylation pathway and rRNA Metabolic Processes. These findings provide novel insights into the molecular regulatory mechanisms underlying meat quality variations among pig breeds.


Assuntos
Perfilação da Expressão Gênica , Músculo Esquelético , Suínos/genética , Animais , Músculo Esquelético/metabolismo , Carne/análise , Redes Reguladoras de Genes , Aminoácidos
2.
Eur J Clin Invest ; 54(8): e14211, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38726889

RESUMO

BACKGROUND: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. RESULTS: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). CONCLUSIONS: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.


Assuntos
HDL-Colesterol , LDL-Colesterol , Estrogênios Conjugados (USP) , Acetato de Medroxiprogesterona , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos , Feminino , Acetato de Medroxiprogesterona/farmacologia , Acetato de Medroxiprogesterona/administração & dosagem , Humanos , Estrogênios Conjugados (USP)/farmacologia , Estrogênios Conjugados (USP)/administração & dosagem , Triglicerídeos/sangue , HDL-Colesterol/efeitos dos fármacos , HDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , Colesterol/sangue , Lipídeos/sangue , Terapia de Reposição de Estrogênios/métodos , Pós-Menopausa/efeitos dos fármacos , Pessoa de Meia-Idade
3.
Org Lett ; 26(23): 4953-4957, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38815137

RESUMO

Organofluorine compounds are of high value in medicinal and agricultural chemistry. Herein, we report a palladium-catalyzed fluoro-alkoxylation of gem-difluoroalkenes for the synthesis of much more challenging sterically hindered ethers. This reaction represents a direct synthesis method for α-trifluoromethyl ethers with a broad functional group tolerance and excellent regioselectivity. This system employs N-fluorobenzenesulfonimide (NFSI) as an electrophilic fluorine source and alcohols as nucleophilic donors, including but not limited to sterically hindered tert-substituted alcohols.

4.
Free Radic Biol Med ; 215: 2-13, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395090

RESUMO

As mitochondrial damage or dysfunction is commonly observed following burn injuries, we investigated whether mitochondrial transplantation (MT) can result in therapeutic benefits in the treatment of burns. Human immortalized epidermal cells (HaCaT) and Kunming mice were used to establish a heat-injured cell model and a deep partial-thickness skin burn animal model, respectively. The cell model was established by exposing HaCaT cells to 45 or 50 °C for 10 min, after which cell proliferation was assayed using fluorescent double-staining and colony formation assays, cell migration was assessed using colloidal gold migration and scratch assays, and cell cycle progression and apoptosis were measured by flow cytometry. Histopathological staining, immunohistochemistry, nick-end labeling analysis, and enzyme-linked immunosorbent assays were used to evaluate the effects of MT on inflammation, tissue recovery, apoptosis, and scar growth in a mouse model. The therapeutic effects were observed in the heat-injured HaCaT cell model. MT promoted cell viability, colony formation, proliferation, and migration; decreased G1 phase; promoted cell division; and decreased apoptosis. Wound-healing promotion, anti-inflammation (decreased mast cell aggregation, down-regulated of TNF-α, IL-1ß, IL-6, and up-regulated IL-10), acceleration of proliferation recovery (up-regulated CD34 and VEGF), apoptosis reduction, and scar formation reduction (decreased collagen I/III ratio and TGF-ß1) were observed in the MT mouse model. The MT mode of action was, however, not investigated in this study. In conclusion, our data indicate that MT exerts a therapeutic effect on burn injuries both in vitro and in vivo.


Assuntos
Queimaduras , Cicatriz , Camundongos , Animais , Humanos , Cicatrização , Pele/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Queimaduras/terapia , Queimaduras/metabolismo
5.
Nat Commun ; 15(1): 6360, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39069515

RESUMO

The fluoroalkyl-containing organic molecules are widely used in drug discovery and material science. Herein, we report ligand regulated nickel(0)-catalyzed regiodivergent hydrosilylation of α-(fluoroalkyl)styrenes without defluorination, providing an atom- and step-economical synthesis route of two types of fluoroalkyl substituted silanes with exclusive regioselectivity. The anti-Markovnikov addition products (ß-fluoroalkyl substituted silanes) are formed with monodentate phosphine ligand. Noteworthy, the bidentate phosphine ligand promote the generation of the more challenging Markovnikov products (α-fluoroalkyl substituted silanes) with tetrasubstituted saturated carbon centers. This protocol features with easy available starting materials and commercially available nickel catalysis, a wide range of substrates and excellent regioselectivity. The structure divergent products undergo a variety of transformations. Comprehensive mechanistic studies including the inverse kinetic isotope effects demonstrate the regioselectivity controlled by ligand structure through α-CF3 nickel intermediate. DFT calculations reveal a distinctive mechanism involving an open-shell singlet state, which is crucial for generating intricate tetra-substituted Markovnikov products.

6.
J Photochem Photobiol B ; 256: 112937, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38743989

RESUMO

As the outermost layer of the human body, the skin suffers from various external factors especially light damage, among which ultraviolet B (UVB) irradiation is common and possesses a relatively high biological damage capacity. Pyroptosis is a newly discovered type of programmed cell death, which can induce cell rupture and induce local inflammatory response. However, the molecular mechanisms of pyroptosis in photodamaged skin is poorly understood. Baicalin, a flavonoid extracted from the desiccated root of Scutellaria baicalensis Georgi (Huang Qin). Despite its antioxidant abilities, whether baicalin protects skin by attenuating UVB-induced pyroptosis remains unclear, which was the aim of this study. The UVB-induced acute skin damage model was established by using human immortalized keratinocytes (HaCaT cells) and Kunming (KM) strain mice. The protective dose selection for baicalin is 50 µM in vitro and 100 mg/kg in vivo. In in vitro study, UVB irradiation significantly decreased cell viability, increased cell death and oxidative stress in HaCaT cells, while pretreatment with baicalin improved these phenomena. Furthermore, the baicalin pretreatment notably suppressed nuclear factor kappa B (NF-κB) translocation, the NLRP3 inflammasome activation and gasdermin D (GSDMD) maturation, thus effectively attenuating UVB-induced pyroptosis. In in vivo study, the baicalin pretreatment mitigated epidermal hyperplasia, collagen fiber fragmentation, oxidative stress and pyroptosis in UVB-irradiated mouse skin. In a nutshell, this study suggests that baicalin could be a potential protective agent to attenuate acute skin damage induced by UVB irradiation through decreasing oxidative stress and suppressing NF-κB/NLRP3/GSDMD-involved pyroptosis.


Assuntos
Flavonoides , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Pele , Raios Ultravioleta , Piroptose/efeitos dos fármacos , Piroptose/efeitos da radiação , Flavonoides/farmacologia , Flavonoides/química , Animais , Humanos , Camundongos , Pele/efeitos da radiação , Pele/efeitos dos fármacos , Pele/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Queratinócitos/metabolismo , Células HaCaT , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Proteínas de Ligação a Fosfato/metabolismo , Inflamassomos/metabolismo , Linhagem Celular
7.
Phytochemistry ; 228: 114241, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39122160

RESUMO

Six pairs of previously undescribed enantiomeric phytocannabinoid-like meroterpenoids, (±)-spinulinoids A‒F, and two naturally occurring compounds, (+)-rhododaurichromanic acid A and (E)-4-((3,7-dimethylocta-2,6-dien-1-yl)oxy)benzoic acid, together with one known congener, (-)-rhododaurichromanic acid A, were obtained from the twigs and leaves of Rhododendron spinuliferum. Their structures were established by their extensive spectral data (NMR and HRESIMS), ECD calculations, and single-crystal X-ray diffraction data. Spinulinoids A and B are unprecedented phytocannabinoid-like meroterpenoids constructed by the resorcinol moiety and a ß-bisabolene unit, whereas spinulinoid C represents a rare adduct of quinone and ß-bisabolene with a tricyclic 6/6/6 ring system.

8.
Med. clín (Ed. impr.) ; 155(7): 295-298, 2020. tab
Artigo em Inglês | IBECS (Espanha) | ID: ibc-192582

RESUMO

INTRODUCTION AND OBJECTIVE: A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension. PATIENTS AND METHOD: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. RESULTS: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. CONCLUSIONS: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms


INTRODUCCIÓN Y OBJETIVO: Un reciente brote de la enfermedad coronavirus 2019 (COVID-19) se produce en todo el mundo. La enzima convertidora de angiotensina 2 (ACE2) puede mediar la entrada del coronavirus en las células huésped. Por lo tanto, se sospechaba que los inhibidores del sistema renina-angiotensina (SRA) contribuían al aumento de la infección por coronavirus. Nos propusimos analizar los efectos de los SRA en los pacientes COVID-19 con hipertensión. PACIENTES Y MÉTODO: En este estudio retrospectivo, de un solo centro, se analizaron 27 pacientes de COVID-19 con hipertensión, que fueron admitidos en el Centro Clínico de Salud Pública de Shangai desde el 25 de enero de 2020 hasta el 31 de enero de 2020, para determinar las características clínicas, los parámetros de laboratorio, los medicamentos y la duración de la estancia. A todos los pacientes se les administró un tratamiento antiviral y antihipertensivo, de los cuales 14 pacientes fueron tratados con SRA y 13 sin SRA. RESULTADOS: Comparando los dos grupos, no encontramos diferencias estadísticamente significativas en los síntomas clínicos y las pruebas de laboratorio. Además, la tos no se agravó. CONCLUSIONES: A través del análisis de esta pequeña muestra, el SRA podría considerarse seguro y eficaz para controlar la presión arterial alta de los pacientes con COVID-19. Es necesario realizar más análisis con una muestra de mayor tamaño para explorar los mecanismos subyacentes


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/terapia , Hipertensão/complicações , Pneumonia Viral/terapia , Pandemias , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Estudos Retrospectivos , Antivirais/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Estatísticas não Paramétricas , Conduta do Tratamento Medicamentoso
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