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Clinical pharmacists participated in the drug therapy of peritonitis caused by Methylobacterium infection in a patient with renal insufficiency. Based on the knowledge of clinical pharmacy, the patient's condition and laboratory parameters, the literature, and the pharmacokinetic/pharmacodynamic characteristics of antibiotics, amikacin in combination with ciprofloxacin was suggested for anti-infection therapy. During the treatment, clinical pharmacists timely evaluated the efficacy of antibiotics, monitored the adverse reactions, and provided individualized pharmaceutical care in the patient.
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Infecciones , Peritonitis , Servicio de Farmacia en Hospital , Insuficiencia Renal , Humanos , Antibacterianos/uso terapéutico , Amicacina/uso terapéutico , Infecciones/complicaciones , Infecciones/tratamiento farmacológico , Insuficiencia Renal/complicaciones , Peritonitis/diagnóstico , Peritonitis/tratamiento farmacológico , Peritonitis/etiología , FarmacéuticosRESUMEN
BACKGROUND: In the continuous endeavor to find safe and efficient treatments for Atopic Dermatitis (AD), there remains a considerable focus on dietary adjustments. Nevertheless, the limited availability of research and conflicting findings in the academic literature pose a hurdle in establishing conclusive recommendations. METHOD: Mendelian randomization (MR) was applied to the most comprehensive genome-wide association studies (GWAS) data on tea intake (447 485), green tea intake (n = 64 949), flavored milk intake (n = 64 941), never eat eggs, dairy, wheat, sugar: Wheat products(n = 461 046), never eat eggs, dairy, wheat, sugar: Sugar or foods/drinks containing sugar (n = 461 046), never eat eggs, dairy, wheat, sugar: I eat all of the above (n = 461 046) and atopic dermatitis (n = 218 467). We used the inverse-variance weighted method (IVW) as the primary method. RESULTS: The IVW analyses have demonstrated an increased tea intake was genetically associated with a reduced risk of AD (odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.430-0.968, p = 0.034). Furthermore, green tea intake was significantly negatively associated with AD (IVW OR: 0.986, 95% CI: 0.975-0.998; p = 0.024) in the IVW model. AD risk could be reduced by never eating wheat products (IVW OR: 8.243E-04, 95% CI: 7.223E-06-9.408E-02, p = 0.003). There was no association between never eating eggs, dairy, wheat, sugar: Sugar, or foods/drinks containing sugar, I eat all of the above and AD. CONCLUSIONS: Our MR study suggests a causal relationship between tea intake, green tea intake, and the avoidance of eating wheat products with atopic dermatitis. Our findings recommend that preventing and managing atopic dermatitis may be achieved by never eating wheat products while increasing tea and green tea intake.
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Dermatitis Atópica , Dieta , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Dermatitis Atópica/genética , Humanos , Dieta/efectos adversos , Té , Huevos , Leche , Triticum/genética , Productos Lácteos , Polimorfismo de Nucleótido SimpleRESUMEN
Economy of Pakistan is heavily dependent upon agriculture and extensive use of pesticide is quiet common to enhance the crop yield. Imidacloprid is among the first choice pesticides in Pakistan and it has been reported that through run off along with water it ends up in water bodies affecting non target aquatic fauna. Through the present investigation, we are reporting the effects of Imidacloprid on the fatty acids composition of a non-target, commercially important carp: Labeo rohita. Fish were exposed to sub lethal concentration of Imidacloprid (120 mgL1) for 2, 4 and 8 days (short term) as well as for 16, 32 and 64 days (long term experimental conditions). Pesticide untreated controls were also maintained for each treatment. Following the specific Imidacloprid exposure, fatty acid composition (%) was determined in the muscle of all experimental groups by using gas chromatography. Fish exposed to Imidacloprid for 8 days had reduced Palmitic acid (p = 0.02) and elevated muscle Arachidic acid (p < 0.001) than control group. Labeo rohita exposed to the pesticide for 32 days had elevated muscle Oleic (p = 0.02) and Linoleic acid (p = 0.02) while fish exposed to Imidacloprid to 64 days had reduced muscle Palmitic (p = 0.04) and Oleic acid (p = 0.03). In conclusion, we are reporting that the exposure to sub lethal concentration of Imidacloprid disturb the muscle fatty acid composition of Labeo rohita that may affect its food quality. The effects were more pronounced under long term experimental conditions and were probably due to potentiating lipid peroxidation and disturbed fish metabolism upon Imidacloprid exposure.
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Cyprinidae , Neonicotinoides , Nitrocompuestos , Plaguicidas , Animales , Ácidos Grasos , Plaguicidas/metabolismo , Músculos , Agua Dulce , Agua/metabolismoRESUMEN
The genetic origins of novelty are of central interest in evolutionary biology. ISG15 and UBA7 are present only in vertebrates. The emergence and evolution of them are not clear. Phylogenetic comparisons revealed that UBA7 descends from gene duplication, and ISG15 and UBA7 arose from UBB/UBC and UBA1, respectively. Uba7 exhibits ubiquitin-activation activity in fish but not tetrapods, suggesting that the relationship of ISG15/Uba7 was promiscuous in origin but was later coopted toward higher specificity. Zebrafish Uba7 is capable of activating the ubiquitin cascade in vitro and in vivo, and it displays distinct specificity preference toward substrates and E2 enzymes compared to zebrafish Uba1. These results together provide a framework for understanding the origin and diversification of ISG15/Uba7 and may serve as a paradigmatic example in which an originally minor functionality in an old gene is made into a new high-specificity protein through random mutations and natural selection.
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Ubiquitinas , Pez Cebra , Animales , Citocinas/genética , Citocinas/metabolismo , Filogenia , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitinas/genética , Ubiquitinas/metabolismo , Pez Cebra/genéticaRESUMEN
Tick and mite infestations pose significant challenges to animal health, agriculture, and public health worldwide. The search for effective and environmentally friendly acaricidal agents has led researchers to explore natural alternatives. In this study, we investigated the acaricidal potential of the Monotheca buxifolia plant extract against Rhipicephalus microplus ticks and Sarcoptes scabiei mites. Additionally, we employed a computational approach to identify phytochemicals from the extract that could serve as drug candidates against these ectoparasites. The contact bioassay results demonstrated that the M. buxifolia plant extract exhibited significant efficacy against R. microplus and S. scabiei, with higher concentrations outperforming the positive control acaricide permethrin in terms of mite mortality. Time exposure to the extract also showed a positive correlation with better lethal concentration (LC50 and LC90) values. Similarly, the adult immersion test revealed a notable inhibition of tick oviposition via the plant extract, especially at higher concentrations. The two-protein primary structure, secondary structure and stability were predicted using the Expasy's ProtParam server, SOPMA and SUSUI server, respectively. Using Homology modeling, the 3D structure of the protein was obtained and validated through the ERRAT server, and active sites were determined through the CASTp server. The docking analysis revealed that Alpha-Amyrenyl acetate and alpha-Tocopherol exhibited the highest docking scores for S. scabiei and R. microplus aspartic protease proteins, respectively. These phytochemicals demonstrated strong binding interactions, suggesting their potential as acaricidal drug candidates. In conclusion, the M. buxifolia plant extract displayed significant acaricidal activity against R. microplus and S. scabiei. Moreover, the computational approach identified promising phytochemicals that could serve as potential drug candidates for controlling these ectoparasites.
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Acaricidas , Rhipicephalus , Animales , Femenino , Sarcoptes scabiei , Larva , Extractos Vegetales/farmacología , Extractos Vegetales/química , Plantas , Fitoquímicos/farmacología , Acaricidas/farmacología , Acaricidas/químicaRESUMEN
To examine the chain mediating role of self-efficacy and hope in the relationship between parental emotion regulation and migrant children's resilience, the study investigated 745 migrant children (mean age = 12.9, SD = 1.5, 371 boys) from four schools and their parents in Guiyang City, Guizhou Province, China. All children were asked to complete the Adolescent Resilience Scale, the General Self-Efficacy Scale, and the Children's Hope Scale. Their parents completed the Parental Emotion Regulation Questionnaire. Structural equation modeling showed that parental emotion regulation could not only directly influence children's resilience but also indirectly influence it through two paths: the independent mediating role of self-efficacy and the chain mediating role of self-efficacy and hope. These findings contribute to a deeper understanding of how parental emotion regulation influences migrant children's resilience and provide important practical guidance for enhancing migrant children's resilience.
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Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of colon and rectum with unknown etiology, and the lesions are mainly confined to the mucosa and submucosa of large intestine. The main clinical features of UC include diarrhea, abdominal pain, bloody purulent stool and tenesmus, which seriously affect patients' quality of life. Most of UC patients would receive drug therapy with the exception of surgery for some severe cases. However, current drugs for the treatment of UC have certain limitations including difficulty of radical treatment, adverse reactions and drug resistance after long-term use and exorbitant price of some drugs. The research and development of new drugs for the treatment of UC is urgent, and natural alkaloids are an important source. This research paid close attention to the progress of natural alkaloids from diverse medicinal plants for treating UC in the last twenty years. The potential mechanisms for the natural alkaloids in the treatment of UC was closely related to its modulation of oxidative stress, immune response, intestinal flora and improvement of the gut barrier function. Remarkable effectiveness and safety of natural-derived alkaloids make them potential candidates of UC therapy.
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Alcaloides/uso terapéutico , Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Animales , HumanosRESUMEN
Human amniotic epithelial cells (hAECs), one of the stem cells identified from the human placenta, possess numerous advantages and have been considered as an attractive and available cell source for regenerative medicine. Accumulating evidence has showed that cellular senescence was one of the pathogenic hubs of diabetic wound chronicity. Keratinocytes and fibroblasts are the primary cells involved in wound healing. Therefore, in this study, we aimed to investigate the anti-senescence effects of hAECs on keratinocytes and fibroblasts in diabetic wounds. Sustained hyperglycemia impaired cell function and accelerated senescence in vitro. However, this phenotype was rescued by hAECs-conditioned medium (hAECs-CM), with increased migration and proliferation in keratinocytes and fibroblasts and enhanced collagen synthesis and α-smooth muscle actin (α-SMA) production in fibroblasts. In addition, hAECs-CM dramatically inhibited intracellular reactive oxygen species (ROS) and senescence-associated ß-galactosidase (SA-ß-gal) in keratinocytes and fibroblasts under high-glucose (HG) condition. Moreover, hAECs-CM could downregulate the increased RAGE and P21 induced by continuous HG stimulation. Intradermal injection of hAECs in diabetic wounds promoted re-epithelialization and granulation tissue formation, accompanied by decreased P21+ cells and increased PCNA+ cells in epidermis and dermis, as well as promoted collagen deposition and α-SMA expression. Furthermore, CM-Dil-labeled hAECs survived to Day 5 but disappeared by Day 10 in diabetic wounds. These findings indicated that hAECs could inhibit diabetes-induced premature senescence and enhance the function of keratinocytes and fibroblasts via paracrine effects, partly by inhibiting RAGE/P21 signaling pathway. Thus, hAECs targeting cellular senescence induced by a hyperglycemic environment may be a new strategy for the treatment of diabetic wounds.
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Diabetes Mellitus , Queratinocitos , Células Cultivadas , Diabetes Mellitus/metabolismo , Fibroblastos/metabolismo , Glucosa/metabolismo , Glucosa/farmacología , Humanos , Queratinocitos/metabolismo , Cicatrización de HeridasRESUMEN
Based on the hybrid functional, we find that at 0 GPa, pristine CsV3Sb5 has a magnetic moment of 0.28 µB per vanadium atom, which is suppressed at a pressure of 2.5 GPa resulting in a spin-crossover. Since the ground state of CsV3Sb5 with charge density wave (CDW) distortion is a non-magnetic state, the magnetic moment of V atoms in pristine CsV3Sb5 will be suppressed by the temperature-induced CDW transition at 94 K. The schematic evolution of magnetic moments as functions of pressure and temperature is presented. At low temperature, CsV3Sb5 is a rare example of materials hosting a pressure-induced magnetic moment, and we suggest that the effects of magnetic moments of V atoms should be considered for understanding its properties.
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Keratin liposomes have emerged as a useful topical drug delivery system given theirenhanced ability to penetrate the skin, making them ideal as topical drug vehicles. However, the mechanisms of the drug penetration enhancement of keratin liposomes have not been clearly elucidated. Therefore, licochalcone A(LA)-loaded skin keratin liposomes (LALs) were prepared to investigate their mechanisms of penetration enhancement on the skin and inB16F10 cells. Skin deposition studies, differential scanning calorimetry (DSC), attenuated total reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and skin distribution and intracellular distribution studies were carried out to demonstrate the drug enhancement mechanisms of LALs. We found that the optimal application of LALs enhanced drug permeation via alterations in the components, structure, and thermodynamic properties of the stratum corneum (SC), that is, by enhancing the lipid fluidization, altering the skin keratin, and changing the thermodynamic properties of the SC. Moreover, hair follicles were the main penetration pathways for the LA delivery, which occurred in a time-dependent manner. In the B16F10 cells, the skin keratin liposomes effectively delivered LA into the cytoplasm without cytotoxicity. Thus, LAL nanoparticles are promising topical drug delivery systems for pharmaceutical and cosmetic applications.
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Liposomas , Absorción Cutánea , Administración Cutánea , Chalconas , Queratinas/metabolismo , Liposomas/química , PielRESUMEN
BACKGROUND: This study aimed to examine changes to optic disc characteristics and macular choroidal microvasculature, and their relationships in young patients with high myopia (HM). METHODS: A total of 90 patients were enrolled in this cross-sectional study. Based on their refractive power, the patients were divided into three groups: 27 in the control group, 34 in the HM group and 29 in the extremely high myopia group. Images of each patient's macula and optic disc were taken by ocular coherence tomography angiography. The macular choroidal and retinal thickness, capillary vessel density and capillary flow area were measured using Matlab software. Parapapillary atrophy (PPA) and the ovality index (OI) obtained from the scanning laser ophthalmoscopy images and the degree of optic disc tilt obtained from the optic nerve head ocular coherence tomography B-scans were analysed by Image J and Matlab software. RESULTS: The PPA area, OI and degree of optic disc tilt were significantly different among the three groups (all p ≤ 0.001). The macular choroidal thickness and microvasculature were significantly different among the three groups (all p < 0.05). Macular choroidal thickness was significantly correlated with PPA area and the degree of optic disc tilt (r = -0.331, p = 0.003; r = -0.394, p = 0.001, respectively). Macular choroidal capillary vessel density and choriocapillaris flow area were associated with PPA area (r = -0.251, p = 0.047; r = -0.326, p = 0.009, respectively). CONCLUSIONS: PPA area, OI and the degree of optic disc tilt were increased in patients with HM, and these changes were correlated with macular choroidal thickness and choroidal microvasculature.
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Miopía , Atrofia Óptica , Disco Óptico , Coroides , Estudios Transversales , Humanos , Microvasos , Tomografía de Coherencia ÓpticaRESUMEN
The incidence of foodborne infections caused by Shigella spp. is still very high in every year, which poses a great potential threat to public health. Conventional quantification methods based on culture techniques, biochemical, and serological identification are time-consuming and labor-intensive. To develop a more rapid and efficient detection method of Shigella spp., we compared the sensitivity and specificity of three different polymerase chain reaction (PCR) methods, including conventional PCR, quantitative real-time PCR (RTQ-PCR), and droplet digital PCR (ddPCR). Our results indicated that ddPCR method exhibited higher sensitivity, and the limit of detection was 10-5 ng/µl for genomic DNA templates, 10-1 cfu/ml for Shigella bacteria culture. In addition, we found that ddPCR was a time-saving method, which required a shorter pre-culturing time. Collectively, ddPCR assay was a reliable method for rapid and effective detection of Shigella spp.
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Disentería Bacilar/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Shigella/genética , Shigella/aislamiento & purificación , Animales , Cartilla de ADN , Disentería Bacilar/microbiología , Heces/microbiología , Límite de Detección , Ratones , Células RAW 264.7 , Sensibilidad y Especificidad , Shigella/patogenicidadRESUMEN
Cryptotanshinone (CPT) is an efficacious acne treatment, while niosomal hydrogel is a known effective topical drug delivery system that produces a minimal amount of irritation. Three-dimensional (3D) printing technologies have the potential to improve the field of personalized acne treatment. Therefore, this study endeavored to develop a 3D-printed niosomal hydrogel (3DP-NH) containing CPT as a topical delivery system for acne therapy. Specifically, CPT-loaded niosomes were prepared using a reverse phase evaporation method, and the formulation was optimized using a response surface methodology. In vitro characterization showed that optimized CPT-loaded niosomes were below 150 nm in size with an entrapment efficiency of between 67 and 71%. The CPT-loaded niosomes were added in a dropwise manner into the hydrogel to formulate CPT-loaded niosomal hydrogel (CPT-NH), which was then printed as 3DP-CPT-NH with specific drug dose, shape, and size using an extrusion-based 3D printer. The in vitro release behavior of 3DP-CPT-NH was found to follow the Korsmeyer-Peppas model. Permeation and deposition experiments showed significantly higher rates of transdermal flux, Q24, and CPT deposition (p < 0.05) compared with 3D-printed CPT-loaded conventional hydrogel (3DP-CPT-CH), which did not contain niosomes. In vivo anti-acne activity evaluated through an acne rat model revealed that 3DP-CPT-NH exhibited a greater anti-acne effect with no skin irritation. Enhanced skin hydration, wide inter-corneocyte gaps in the stratum corneum and a disturbed lipid arrangement may contribute towards the enhanced penetration properties of CPT. Collectively, this study demonstrated that 3DP-CPT-NH is a promising topical drug delivery system for personalized acne treatments.
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Acné Vulgar/tratamiento farmacológico , Hidrogeles/química , Fenantrenos/administración & dosificación , Administración Cutánea , Animales , Sistemas de Liberación de Medicamentos/métodos , Liposomas/farmacología , Masculino , Tamaño de la Partícula , Fenantrenos/química , Impresión Tridimensional , Ratas , Piel/metabolismo , Absorción CutáneaRESUMEN
We have developed an iron-catalyzed direct olefination for enaminone synthesis, with saturated ketones as a source of olefins. This direct ketone ß-functionalization reaction has readily available starting materials and a wide range of substrates and requires mild reaction conditions.
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BACKGROUND: The aim of this study was to investigate the occupational stress and hypertension in desert petroleum workers in Xinjiang, and to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. METHODS: Using cluster sampling, 1280 desert petroleum workers of 3 petroleum fields in Xinjiang Karamay were randomly selected as the target group for this study. According to the inclusion criteria, a total of 1080 workers were included as the baseline for this study. We followed these workers for 2 years to investigate their occupational stress and hypertension. The polymorphism of GR gene was detected by polymerase chain reaction-restriction fragment length polymorphism. We applied appropriate statistical methods to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. RESULTS: After 2 years of follow-up, there were 995 desert petroleum workers in the queue. The study showed that the incidence of hypertension in desert petroleum workers were 19.4%. Compared with the baseline data, the level of occupational stress increased, and with the increase of occupational stress, the incidence of hypertension was gradually increasing. A positive relationship was observed in the GR BCL1 gene polymorphisms and hypertension. Relative to the CC genotype, carries of the GG genotype had a significantly higher risk of hypertension (OR = 2.830). With the combination of genotype CG and GG, carries of CG and GG increased the risk of hypertension (adjusted OR = 2.238, 95%CI:1.104-4.940). There was no significant association between GR G678S gene polymorphisms and hypertension. CONCLUSION: GR gene polymorphism and occupational stress of desert petroleum workers were important risk factors for hypertension.
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Hipertensión/genética , Estrés Laboral/genética , Industria del Petróleo y Gas , Polimorfismo Genético , Receptores de Glucocorticoides/genética , Adulto , China/epidemiología , Clima Desértico , Femenino , Estudios de Seguimiento , Expresión Génica , Genotipo , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Hipertensión/psicología , Incidencia , Masculino , Persona de Mediana Edad , Estrés Laboral/epidemiología , Estrés Laboral/fisiopatología , Estrés Laboral/psicología , Ocupaciones , Polimorfismo de Longitud del Fragmento de Restricción , Factores de RiesgoRESUMEN
Activity and half-life play key roles in the application of GHRH analogues. The GHRH monomers produced in a solid synthesizer were incubated, respectively, in NH4OH solution and lyophilized to obtain their dimers. The activities, specificities, and receptor affinities of the GHRH dimers were evaluated in rGH release/inhibition, rACTH/LH/PRL release, pituitary homogenate binding, and fluorescent staining. Compared to hGHRH(1-44)NH2 (S), PP-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-PP (2D), P-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-P (2E), (1)P-hGHRH(2-44)-GGC-CGG-hGHRH(44-2)-(1)P (2F), or hGHRH(1-44)-GGC-CGG-hGHRH(44-1) (2Y) had potency of 104 ± 16.7%, 94 ± 32.6%, 114 ± 16.6%, or 122 ± 14.5% and similar specificities. The inhibition effect of GHIH on rGH stimulated by GHRH dimer was in dose-/time-dependent manner. The staining of FITC-labeled dimer showed cytomembrane distribution and the binding ranking was 2F>2D>2Y>2E>S. 2F presents the strongest activity and the highest affinity to pituitary cells. The dimer with (1)Pro-GHRH stimulates stronger rGH release than that with (1)Tyr-GHRH and the N-terminal single cyclic amino acid is required for the stimulation.
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Hormona Liberadora de Hormona del Crecimiento/análogos & derivados , Hormona Liberadora de Hormona del Crecimiento/química , Animales , Membrana Celular/metabolismo , Femenino , Colorantes Fluorescentes/química , Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/síntesis química , Hormonas/metabolismo , Humanos , Ligandos , Fragmentos de Péptidos/química , Hipófisis/metabolismo , Unión Proteica , Multimerización de Proteína , Estructura Terciaria de Proteína , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/químicaRESUMEN
Some theories posit a close relationship between social anxiety and problematic social media use; however, empirical findings are inconsistent, and existing hypotheses are conflicting. Hence, we conducted a systematic review and meta-analysis to clarify the relationship between social anxiety and problematic social media use. After searching and screening the literature, we identified 53 studies, including 59,928 participants and 56 effect sizes, for analysis. A meta-analysis was subsequently performed using CMA software. Results showed that social anxiety and problematic social media use were highly positively correlated. The moderating effect results suggested that the relationship between social anxiety and problematic social media use was influenced by the measurement instrument, sex, publication year, and platform type; however, the relationship was not moderated by region and age. It is suggested to consider social anxiety in the treatment of problematic social media use.
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Trastorno de Adicción a Internet , Medios de Comunicación Sociales , Humanos , Trastorno de Adicción a Internet/psicología , Trastorno de Adicción a Internet/epidemiología , Ansiedad/psicología , Ansiedad/epidemiología , Fobia Social/psicología , Fobia Social/epidemiologíaRESUMEN
Parenting styles influence child development. Some theories and numerous studies have shown a close relationship between parenting style and youths' subjective well-being; however, the results of different studies were inconsistent. Hence, our meta-analysis aimed to determine the overall relationship between positive and negative parenting styles on subjective well-being (including life satisfaction, positive and negative affect) and any moderating effects between them. After searching and screening the literature, 155 studies were included in the analysis, comprising 79,979 participants and 417 effect sizes. The results showed that positive parenting style was significantly positively associated with subjective well-being (r = .318, 95% CI = .287 to .348), life satisfaction (r = .358, 95% CI = .326 to .389), and positive affect (r = .355, 95% CI = .303 to .406), but significantly negatively associated with negative affect (r = -.153, 95% CI = -.207 to -.098). Negative parenting style was significantly negatively related to subjective well-being (r = -.173, 95% CI = -.205 to -.152), life satisfaction (r = -.144, 95% CI = -.175 to -.112), and positive affect (r = -.078, 95% CI = -.129 to -.027), but significantly positively related to negative affect (r = .204, 95% CI = .149 to .257). Moderating effect results showed that the relationship between parenting style and subjective well-being is moderated by age, gender, and cultural background. Findings highlight the benefits of positive parenting styles in promoting healthy child development and well-being.
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Nano-particles demonstrating excellent anticancer properties have gradually found application in cancer therapy. However, their widespread use is impeded by their potential toxicity, high cost, and the complexity of the preparation process. In this study, we achieved exosome-like Centella asiatica-derived nanovesicles (ADNVs) through a straightforward juicing and high-speed centrifugation process. We employed transmission electron microscopy and nanoparticle flow cytometry to characterize the morphology, diameter, and stability of the ADNVs. We evaluated the in vitro anticancer effects of ADNVs using Cell Counting Kit-8 and apoptosis assays. Through sequencing and bicinchoninic acid protein analysis, we discovered the abundant presence of proteins and microRNAs in ADNVs. These microRNAs can target various diseases such as cancer and infection. Furthermore, we demonstrated the effective internalization of ADNVs by HepG2 cells, resulting in an increase in reactive oxygen species levels, mitochondrial damage, cell cycle arrest at the G1 phase, and apoptosis. Finally, we analyzed changes in cellular metabolites post-treatment using cell metabolomics techniques. Our findings indicated that ADNVs primarily influence metabolic pathways such as amino acid metabolism and lipid biosynthesis, which are closely associated with HepG2 treatment. Our results demonstrate the potential utility of ADNVs as anticancer agents.
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Apoptosis , Proliferación Celular , Centella , Exosomas , Metabolómica , Nanopartículas , Extractos Vegetales , Triterpenos , Humanos , Células Hep G2 , Centella/química , Proliferación Celular/efectos de los fármacos , Exosomas/metabolismo , Exosomas/efectos de los fármacos , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Triterpenos/farmacología , Triterpenos/química , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , MicroARNs/metabolismo , MicroARNs/genéticaRESUMEN
Objective: Numerous studies have reported that metformin can reduce the risk of tumor development. However, some of the results of these studies are conflicting, necessitating a more reliable evaluation. Methods: We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis. Results: MR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae. Conclusion: Metformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings.