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1.
Sci Rep ; 14(1): 16033, 2024 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992112

RESUMEN

The association between the triglyceride-glucose (TyG) index and impaired fasting glucose (IFG) in elderly individuals remains uncertain. Our study aimed to explore the association between the TyG index and the risk of future IFG in this population. This retrospective cohort study included 17,746 elderly individuals over 60. In this population, Cox regression models proportional to hazards, along with smooth curve fitting and cubic spline functions, were employed to examine the association between the baseline TyG index and the risk of IFG. Subgroup analyses and sensitivity were also performed to ensure the robustness of the study findings. After adjusting for covariates, a positive association between the TyG index and the risk of IFG was found (HR = 1.43, 95% CI 1.27-1.60, P < 0.0001). The likelihood of IFG rose steadily as the TyG index quartiles (from Q1 to Q4) increased, with Q4 demonstrating a 62% elevated risk compared to Q1 (adjusted HR = 1.62, 95% CI 1.37-1.90). Additionally, we found the association between TyG index and risk of IFG was a linear. Sensitivity and subgroup analyses confirmed the stability of the results. Our study observed a linear association between the TyG index and the development of IFG in elderly Chinese individuals. Recognizing this association can help clinicians identify high-risk individuals and implement targeted interventions to reduce their risk of progressing to diabetes.


Asunto(s)
Glucemia , Ayuno , Triglicéridos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/análisis , China/epidemiología , Pueblos del Este de Asia , Ayuno/sangre , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Triglicéridos/sangre
2.
Vaccines (Basel) ; 12(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39066379

RESUMEN

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.

3.
bioRxiv ; 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38883723

RESUMEN

The arginine vasopressin 1b receptor (Avpr1b) plays an important role in social behaviors including social learning, memory, and aggression, and is known to be a specific marker for the cornu ammonis area 2 (CA2) regions of the hippocampus. The fasciola cinereum (FC) is an anatomical region in which Avpr1b expressing neurons are prominent, but the functional roles of the FC have yet to be investigated. Surprisingly, the FC is absent in the inbred BTBR T+tf/J (BTBR) mouse strain used to study core behavioral deficits of autism. Here, we characterized and compared transcriptomic expression profiles using single nucleus RNA sequencing and identified 7 different subpopulations and heterogeneity within the dorsal CA2 (dCA2) and FC. Mef2c, involved in autism spectrum disorder, is more highly expressed in the FC. Using Hiplex in situ hybridization, we examined the neuroanatomical locations of these subpopulations in the proximal and distal regions of the hippocampus. Anterograde tracing of Avpr1b neurons specific for the FC showed projections to the IG, dCA2, lacunosum molecular layer of CA1, dorsal fornix, septofibrial nuclei, and intermediate lateral septum (iLS). In contrast to the dCA2, inhibition of Avpr1b neurons in the FC by the inhibitory DREADD system during behavioral testing did not impair social memory. We performed single nucleus RNA sequencing in the dCA2 region and compared between wildtype (WT) and BTBR mice. We found that transcriptomic profiles of dCA2 neurons between BTBR and WT mice are very similar as they did not form any unique clusters; yet, we found there were differentially expressed genes between the dCA2s of BTBR and WT mice. Overall, this is a comprehensive study of the comparison of Avpr1b neuronal subpopulations between the FC and dCA2. The fact that FC is absent in BTBR mice, a mouse model for autism spectrum disorder, suggests that the FC may play a role in understanding neuropsychiatric disease.

4.
Endocrine ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850440

RESUMEN

AIM: Tirzepatide, a newly developed dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has received approval for treating type 2 diabetes (T2D) and is currently being studied for its potential in long-term weight control. We aim to explore the safety and efficacy of once-weekly subcutaneous tirzepatide for weight loss in T2D or obese patients. METHODS: A comprehensive search was performed on various databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception up to April 29, 2024, to identify randomized controlled trials (RCTs) that assessed the efficacy of once-weekly tirzepatide compared to a placebo in adults with or without T2D. The mean difference (MD) and risk ratio (RR) were calculated for continuous and dichotomous outcomes, respectively. The risk of bias was evaluated using the RoB-2 tool (Cochrane), while the statistical analysis was conducted utilizing RevMan 5.4.1 software. RESULTS: Seven RCTs comprising 4795 individuals ranging from 12 to 72 weeks were identified. Compared to the placebo group, tirzepatide at doses of 5, 10, and 15 mg demonstrated significant dose-dependent weight loss. The mean difference (MD) in the percentage change in body weight (BW) was -8.07% (95% CI -11.01, -5.13; p < 0.00001), -10.79% (95% CI -13.86, -7.71; p < 0.00001), and -11.83% (95% CI -14.52, -9.14; p < 0.00001), respectively. Additionally, the MD in the absolute change in BW was -7.5 kg (95% CI -10.9, -4.1; p < 0.0001), -11.0 kg (95% CI -16.9, -5.2; p = 0.0002), and -11.5 kg (95% CI -16.2, -6.7; p < 0.00001), for the 5, 10, and 15 mg doses, respectively. All three doses of tirzepatide also significantly reduced body mass index and waist circumference. Furthermore, it led to a greater percentage of patients experiencing weight loss exceeding 5, 10, 15, 20, and 25%. Moreover, tirzepatide showed great success in reducing blood pressure, blood sugar levels, and lipid profiles. In terms of safety, gastrointestinal side effects were the most frequently reported adverse events in all three doses of tirzepatide groups, which were generally mild-to-moderate and transient. CONCLUSION: Tirzepatide treatment could lead to remarkable and sustained weight loss that is well-tolerated and safe, representing a novel and valuable therapeutic strategy for long-term weight management.

5.
J Environ Manage ; 359: 121044, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38714035

RESUMEN

Dams and reservoirs have significantly altered river flow dynamics worldwide. Accurately representing reservoir operations in hydrological models is crucial yet challenging. Detailed reservoir operation data is often inaccessible, leading to relying on simplified reservoir operation modules in most hydrological models. To improve the capability of hydrological models to capture flow variability influenced by reservoirs, this study proposes a hybrid hydrological modeling framework, which combines a process-based hydrological model with a machine-learning-based reservoir operation module designed to simulate runoff under reservoir operations. The reservoir operation module employs an ensemble of three machine learning models: random forest, support vector machine, and AutoGluon. These models predict reservoir outflows using precipitation and temperature data as inputs. The Soil and Water Assessment Tool (SWAT) then integrates these outflow predictions to simulate runoff. To evaluate the performance of this hybrid approach, the Xijiang Basin within the Pearl River Basin, China, is used as a case study. The results highlight the superiority of the SWAT model coupled with machine learning-based reservoir operation models compared to alternative modeling approaches. This hybrid model effectively captures peak flows and dry period runoff. The Nash-Sutcliffe Efficiency (NSE) in daily runoff simulations shows substantial improvement, ranging from 0.141 to 0.780, with corresponding enhancements in the coefficient of determination (R2) by 0.098-0.397 when compared to the original reservoir operation modules in SWAT. In comparison to parameterization techniques lacking a dedicated reservoir module, NSE enhancements range from 0.068 to 0.537, and R2 improvements range from 0.027 to 0.139. The proposed hybrid modeling approach effectively characterizes the impact of reservoir operations on river flow dynamics, leading to enhanced accuracy in runoff simulation. These findings offer valuable insights for hydrological forecasting and water resources management in regions influenced by reservoir operations.


Asunto(s)
Hidrología , Aprendizaje Automático , Modelos Teóricos , Ríos , Humanos , China , Movimientos del Agua
7.
J Transl Int Med ; 12(2): 197-208, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38779116

RESUMEN

Background and Objectives: The Alberta Stroke Program CT Score (ASPECTS) is a widely used rating system for assessing infarct extent and location. We aimed to investigate the prognostic value of ASPECTS subregions' involvement in the long-term functional outcomes of acute ischemic stroke (AIS). Materials and Methods: Consecutive patients with AIS and anterior circulation large-vessel stenosis and occlusion between January 2019 and December 2020 were included. The ASPECTS score and subregion involvement for each patient was assessed using posttreatment magnetic resonance diffusion-weighted imaging. Univariate and multivariable regression analyses were conducted to identify subregions related to 3-month poor functional outcome (modified Rankin Scale scores, 3-6) in the reperfusion and medical therapy cohorts, respectively. In addition, prognostic efficiency between the region-based ASPECTS and ASPECTS score methods were compared using receiver operating characteristic curves and DeLong's test. Results: A total of 365 patients (median age, 64 years; 70% men) were included, of whom 169 had poor outcomes. In the reperfusion therapy cohort, multivariable regression analyses revealed that the involvement of the left M4 cortical region in left-hemisphere stroke (adjusted odds ratio [aOR] 5.39, 95% confidence interval [CI] 1.53-19.02) and the involvement of the right M3 cortical region in right-hemisphere stroke (aOR 4.21, 95% CI 1.05-16.78) were independently associated with poor functional outcomes. In the medical therapy cohort, left-hemisphere stroke with left M5 cortical region (aOR 2.87, 95% CI 1.08-7.59) and caudate nucleus (aOR 3.14, 95% CI 1.00-9.85) involved and right-hemisphere stroke with right M3 cortical region (aOR 4.15, 95% CI 1.29-8.18) and internal capsule (aOR 3.94, 95% CI 1.22-12.78) affected were related to the increased risks of poststroke disability. In addition, region-based ASPECTS significantly improved the prognostic efficiency compared with the conventional ASPECTS score method. Conclusion: The involvement of specific ASPECTS subregions depending on the affected hemisphere was associated with worse functional outcomes 3 months after stroke, and the critical subregion distribution varied by clinical management. Therefore, region-based ASPECTS could provide additional value in guiding individual decision making and neurological recovery in patients with AIS.

9.
Vaccines (Basel) ; 12(2)2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38400201

RESUMEN

The authors would like to make the following corrections to this published paper [...].

11.
Nat Immunol ; 25(2): 307-315, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38182667

RESUMEN

The global outbreak of the mpox virus (MPXV) in 2022 highlights the urgent need for safer and more accessible new-generation vaccines. Here, we used a structure-guided multi-antigen fusion strategy to design a 'two-in-one' immunogen based on the single-chain dimeric MPXV extracellular enveloped virus antigen A35 bivalently fused with the intracellular mature virus antigen M1, called DAM. DAM preserved the natural epitope configuration of both components and showed stronger A35-specific and M1-specific antibody responses and in vivo protective efficacy against vaccinia virus (VACV) compared to co-immunization strategies. The MPXV-specific neutralizing antibodies elicited by DAM were 28 times higher than those induced by live VACV vaccine. Aluminum-adjuvanted DAM vaccines protected mice from a lethal VACV challenge with a safety profile, and pilot-scale production confirmed the high yield and purity of DAM. Thus, our study provides innovative insights and an immunogen candidate for the development of alternative vaccines against MPXV and other orthopoxviruses.


Asunto(s)
Monkeypox virus , Vacunas , Animales , Ratones , Proteínas del Envoltorio Viral , Anticuerpos Antivirales , Virus Vaccinia , Antígenos Virales , Inmunidad
12.
Virulence ; 15(1): 2301242, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38170681

RESUMEN

Influenza A virus (IAV) poses a threat to patients receiving immunosuppressive medications since they are more susceptible to infection with severe symptoms, and even death. Understanding the direct effects of immunosuppressants on IAV infection is critical for optimizing immunosuppression in these patients who are infected or at risk of influenza virus infection. We profiled the effects of 10 immunosuppressants, explored the antiviral mechanisms of immunosuppressants, and demonstrated the combined effects of immunosuppressants with the antiviral drug oseltamivir in IAV-infected cell models. We found that mycophenolic acid (MPA) strongly inhibits viral RNA replication via depleting cellular guanosine pool. Treatment with 6-Thioguanine (6-TG) promoted viral protein degradation through a proteasomal pathway. Filgotinib blocked mRNA splicing of matrix protein 2, resulting in decreased viral particle assembly. Furthermore, combined treatment with immunosuppressants and oseltamivir inhibits IAV viral particle production in an additive or synergic manner. Our results suggest that MPA, 6-TG, and filgotinib could be the preferential choices for patients who must take immunosuppressants but are at risk of influenza virus infection.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Humanos , Oseltamivir/farmacología , Antivirales/farmacología , Gripe Humana/tratamiento farmacológico , Inmunosupresores/farmacología , Virus de la Influenza A/fisiología , Replicación Viral , ARN Mensajero , Estabilidad Proteica
13.
Environ Sci Technol ; 58(2): 1119-1130, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38175796

RESUMEN

The severe water scarcity in China poses significant economic risks to its agriculture, energy, and manufacturing sectors, which can have a cascading effect through the supply chains. Current research has assessed water scarcity losses for global countries and Chinese provinces by using the water scarcity risk (WSR) method. However, this method involves subjective functions and parameter settings, and it fails to capture the adaptive behaviors of economies to water scarcity, compromising the reliability of quantified water scarcity loss. There is a pressing need for a new method to assess losses related to water scarcity. Here, we develop an agent-based complex network model to estimate the inter-regional and intersectoral impacts of water scarcity on both cities and basins. Subsequently, we evaluate the supply chain-wide economic benefits of four different water conservation measures as stipulated by the 14th Five-Year Plan for the Construction of a Water-Saving Society. These measures include increasing the utilization rate of recycled water in water-scarce cities, reducing the national water consumption per industrial value-added, and implementing agricultural and residential water conservation measures. Results show that direct losses constitute only 9% of the total losses from water scarcity. Approximately 37% of the losses can be attributed to interregional impacts. Among the water-scarce cities, Qingdao, Lanzhou, Jinan, and Zhengzhou pose a significant threat to China's supply chains. Agricultural water conservation yields the highest amount of water savings and economic benefits, while residential water conservation provides the highest economic benefit per unit of water saved. The results provide insights into managing water scarcity, promoting cross-regional cooperation, and mitigating economic impacts.


Asunto(s)
Conservación de los Recursos Hídricos , Abastecimiento de Agua , Reproducibilidad de los Resultados , Inseguridad Hídrica , China , Agricultura , Agua
14.
Emerg Microbes Infect ; 13(1): 2284297, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37970736

RESUMEN

Following the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (-3.74%-10.75%) in the one-dose cohort and 72.19% (57.33%-81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Rociadores Nasales , Pandemias , China , Anticuerpos Monoclonales , Anticuerpos ampliamente neutralizantes , Anticuerpos Neutralizantes , Anticuerpos Antivirales
15.
Diabetes Obes Metab ; 26(3): 911-923, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38016699

RESUMEN

AIM: To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals. METHODS: A thorough search was performed of various databases including PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrials.gov, CNKI and Wanfang from their inception up to April 11, 2023. Our aim was to identify randomized controlled trials (RCTs) that compared the efficacy of semaglutide administered once weekly with placebo in overweight or obese adults. Through a review of the literature, data were extracted from relevant studies and assessed for quality, and a meta-analysis was conducted using RevMan 5.4.1 software. RESULTS: Six RCTs comprising 3962 overweight or obese individuals were identified. The findings indicated that, in comparison to the placebo group, semaglutide caused a significant and sustainable reduction in the percentage of body weight (BW; mean difference [MD]: -11.80% [95% confidence interval {CI} -12.93, -10.68]; P < 0.00001) as well as a decrease in absolute BW (MD: -12.2 kg [95% CI -13.3, -11.1]; P < 0.00001), body mass index (MD: -4.5 kg/m2 [95% CI -4.9, -4.1]; P < 0.00001) and waist circumference (MD:-9.4 cm [95% CI -10.1, -8.8]; P < 0.00001). Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Furthermore, semaglutide showed significant efficacy in controlling blood pressure, blood sugar levels, C-reactive protein levels, and lipid profiles. In terms of safety, the most common adverse effects following semaglutide treatment were gastrointestinal adverse reactions (risk ratio: 1.49 [95% CI 1.38, 1.60]; P < 0.00001), which were generally mild to moderate in severity and temporary. CONCLUSION: In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.


Asunto(s)
Diabetes Mellitus , Sobrepeso , Adulto , Humanos , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Sobrepeso/inducido químicamente , Hipoglucemiantes/efectos adversos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/inducido químicamente , Diabetes Mellitus/tratamiento farmacológico , Pérdida de Peso , Péptidos Similares al Glucagón/efectos adversos
16.
Mol Neurobiol ; 61(1): 385-396, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37612480

RESUMEN

Postpartum depression is a serious disease with a high incidence and severe impact on pregnant women and infants, but its mechanism remains unclear. Recent studies have shown that GABA receptors, especially extrasynaptic receptors, are closely associated with postpartum depression. There are many different structures of GABA receptors, so different types of receptors have different functions, even though they transmit information primarily through GABA. In this review, we focus on the function of GABA receptors, especially extrasynaptic GABA receptors, and their association with postpartum depression. We have shown that the extrasynaptic GABA receptor has a significant impact on the activity and function of neurons through tonic inhibition. The extrasynaptic receptor and its ligands undergo drastic changes during pregnancy and childbirth. Abnormal changes or the body's inability to adjust and recover may be an important cause of postpartum depression. Finally, by reviewing the mechanisms of several novel antidepressants, we suggest that extrasynaptic receptors may be potential targets for the treatment of postpartum depression.


Asunto(s)
Depresión Posparto , Receptores de GABA , Embarazo , Femenino , Humanos , Receptores de GABA-A , Neuronas/fisiología
17.
Am J Surg Pathol ; 48(3): 251-265, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38108373

RESUMEN

Tumor budding (TB) is a powerful prognostic factor in colorectal cancer (CRC). An internationally standardized method for its assessment (International Tumor Budding Consensus Conference [ITBCC] method) has been adopted by most CRC pathology protocols. This method requires that TB counts are reported by field area (0.785 mm 2 ) rather than objective lens and a normalization factor is applied for this purpose. However, the validity of this approach is yet to be tested. We sought to validate the ITBCC method with a particular emphasis on normalization as a tool for standardization. In a cohort of 365 stage I-III CRC, both normalized and non-normalized TB were significantly associated with disease-specific survival and recurrence-free survival ( P <0.0001). Examining both 0.95 and 0.785 mm 2 field areas in a subset of patients (n=200), we found that normalization markedly overcorrects TB counts: Counts obtained in a 0.95 mm 2 hotspot field were reduced by an average of 17.5% following normalization compared with only 3.8% when counts were performed in an actual 0.785 mm 2 field. This resulted in 45 (11.3%) cases being downgraded using ITBCC grading criteria following normalization, compared with only 5 cases (1.3%, P =0.0007) downgraded when a true 0.785 mm 2 field was examined. In summary, the prognostic value of TB was retained regardless of whether TB counts in a 0.95 mm 2 field were normalized. Normalization resulted in overcorrecting TB counts with consequent downgrading of most borderline cases. This has implications for risk stratification and adjuvant treatment decisions, and suggests the need to re-evaluate the role of normalization in TB assessment.


Asunto(s)
Neoplasias Colorrectales , Humanos , Estadificación de Neoplasias , Pronóstico , Clasificación del Tumor , Neoplasias Colorrectales/patología , Consenso
18.
Hum Vaccin Immunother ; 19(2): 2263228, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37843437

RESUMEN

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.


Asunto(s)
Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Humanos , Lactante , Anticuerpos Antivirales , Método Doble Ciego , Pueblos del Este de Asia , Inmunogenicidad Vacunal , Inmunoglobulina A , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/efectos adversos , Vacunas contra Rotavirus/uso terapéutico , Vacunas Atenuadas , Vacunas Combinadas
19.
PeerJ ; 11: e16077, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37744241

RESUMEN

Background: Madin-Darby canine kidney (MDCK) cells are a cellular matrix in the production of influenza vaccines. The proliferation rate of MDCK cells is one of the critical factors that determine the vaccine production cycle. It is yet to be determined if there is a correlation between cell proliferation and alterations in metabolic levels. This study aimed to explore the metabolic differences between MDCK cells with varying proliferative capabilities through the use of both untargeted and targeted metabolomics. Methods: To investigate the metabolic discrepancies between adherent cell groups (MDCK-M60 and MDCK-CL23) and suspension cell groups (MDCK-XF04 and MDCK-XF06), untargeted and targeted metabolomics were used. Utilizing RT-qPCR analysis, the mRNA expressions of key metabolites enzymes were identified. Results: An untargeted metabolomics study demonstrated the presence of 81 metabolites between MDCK-M60 and MDCK-CL23 cells, which were mainly affected by six pathways. An analysis of MDCK-XF04 and MDCK-XF06 cells revealed a total of 113 potential metabolites, the majority of which were impacted by ten pathways. Targeted metabolomics revealed a decrease in the levels of choline, tryptophan, and tyrosine in MDCK-CL23 cells, which was in accordance with the results of untargeted metabolomics. Additionally, MDCK-XF06 cells experienced a decrease in 5'-methylthioadenosine and tryptophan, while S-adenosylhomocysteine, kynurenine, 11Z-eicosenoic acid, 3-phosphoglycerate, glucose 6-phosphate, and phosphoenolpyruvic acid concentrations were increased. The mRNA levels of MAT1A, MAT2B, IDO1, and IDO2 in the two cell groups were all increased, suggesting that S-adenosylmethionine and tryptophan may have a significant role in cell metabolism. Conclusions: This research examines the effect of metabolite fluctuations on cell proliferation, thus offering a potential way to improve the rate of MDCK cell growth.


Asunto(s)
Metabolómica , Triptófano , Animales , Perros , Células de Riñón Canino Madin Darby , Carcinogénesis , Proliferación Celular , Riñón
20.
Biologicals ; 83: 101697, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37579524

RESUMEN

MDCK is currently the main cell line used for influenza vaccine production in culture. Previous studies have reported that MDCK cells possess tumorigenic ability in nude mice. Although complete cell lysis can be ensured during vaccine production, host cell DNA released after cell lysis may still pose a risk for tumorigenesis. Greater caution is needed in the production of human vaccines; therefore, the use of gene editing to establish cells incapable of forming tumors may significantly improve the safety of influenza vaccines. Knowledge regarding the genes and molecular mechanisms that affect the tumorigenic ability of MDCK cells is crucial; however, our understanding remains superficial. Through monoclonal cell screening, we previously obtained a cell line, CL23, that possesses significantly reduced cell proliferation, migration, and invasion abilities, and tumor-bearing experiments in nude mice showed the absence of tumorigenic cells. With a view to exploring tumorigenesis-related genes in MDCK cells, DIA proteomics was used to compare the differences in protein expression between wild-type (M60) and non-tumorigenic (CL23) cells. Differentially expressed proteins were verified at the mRNA level by RT-qPCR, and a number of genes involved in cell tumorigenesis were preliminarily screened. Immunoblotting further confirmed that related protein expression was significantly reduced in non-tumorigenic cells. Inhibition of CDC20 expression by RNAi significantly reduced the proliferation and migration of MDCK cells and increased the proliferation of the influenza virus; therefore, CDC20 was preliminarily determined to be an effective target gene for the inhibition of cell tumorigenicity. These results contribute to a more comprehensive understanding of the mechanism underlying cell tumorigenesis and provide a basis for the establishment of target gene screening in genetically engineered non-tumorigenic MDCK cell lines.


Asunto(s)
Vacunas contra la Influenza , Ratones , Animales , Perros , Humanos , Células de Riñón Canino Madin Darby , Ratones Desnudos , Línea Celular , Carcinogénesis/genética , Proteínas Cdc20
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