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BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.
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Becaplermina , Dieta Hiperlipídica , Células Endoteliais , Hipocampo , Síndrome Metabólica , Microglia , Transcitose , Animais , Camundongos , Becaplermina/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Transcitose/fisiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Microglia/metabolismo , Microglia/patologia , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Masculino , Osso e Ossos/metabolismo , Osso e Ossos/patologiaRESUMO
Tipping points or critical transitions widely exist during the progression of many biological processes. It is of great importance to detect the tipping point with the measured omics data, which may be a key to achieving predictive or preventive medicine. We present the tipping point detector (TPD), a web tool for the detection of the tipping point during the dynamic process of biological systems, and further its leading molecules or network, based on the input high-dimensional time series or stage course data. With the solid theoretical background of dynamic network biomarker (DNB) and a series of computational methods for DNB detection, TPD detects the potential tipping point/critical state from the input omics data and outputs multifarious visualized results, including a suggested tipping point with a statistically significant P value, the identified key genes and their functional biological information, the dynamic change in the DNB/leading network that may drive the critical transition and the survival analysis based on DNB scores that may help to identify 'dark' genes (nondifferential in terms of expression but differential in terms of DNB scores). TPD fits all current browsers, such as Chrome, Firefox, Edge, Opera, Safari and Internet Explorer. TPD is freely accessible at http://www.rpcomputationalbiology.cn/TPD.
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Internet , Biomarcadores/metabolismoRESUMO
INTRODUCTION/AIMS: Many small-sized, single-center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this meta-analysis are to review and contrast the effects of various types of stem cells in in vivo models used to reconstruct peripheral nerve injuries (PNIs) and to assess the reliability and stability of the available evidence. METHODS: A systematic search was conducted using Cochrane Library, Embase, PubMed, and Web of Science to identify studies conducted from January 1, 2000, to September 21, 2022, and investigate stem cell therapy in peripheral nerve reconstruction animal models. Studies that met the relevant criteria were deemed eligible for this meta-analysis. RESULTS: Fifty-five preclinical studies with a total of 1234 animals were incorporated. Stem cells demonstrated a positive impact on peripheral nerve regeneration at different follow-up times in the forest plots of five outcome indicators: compound muscle action potential (CMAP) amplitude, latency, muscle mass ratio, nerve conduction velocity, and sciatic functional index (SFI). In most comparisons, stem cell groups showed substantial differences compared with the control groups. The superior performance of adipose-derived stem cells (ADSCs) in terms of SFI, CMAP amplitude, and latency (p < .001) was identified. DISCUSSION: The findings consistently demonstrated a favorable outcome in the reconstruction process when utilizing different groups of stem cells, as opposed to control groups where stem cells were not employed.
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Traumatismos dos Nervos Periféricos , Células-Tronco , Animais , Regeneração Nervosa/fisiologia , Reprodutibilidade dos TestesRESUMO
Objective: To assess the effect of Traditional Chinese Medicine (TCM) nutrition treatment (Bushenhuoxue nutritional decoction) in overweight patients with polycystic ovary syndrome (PCOS). Methods: Retrospective analysis of 96 overweight patients with PCOS who received treatment in our hospital from October 2020 to June 2022 was done. Among them, 46 patients received routine drug treatment and daily dietary intervention (control group), while 50 patients received additional TCM nutrition support in addition to routine treatment (observation group). Glucose and lipid metabolism indicators and hormone levels were compared between the two groups before and after the treatment. Ovulation rate, pregnancy rate, and adverse reactions were compared between both groups one year after the treatment. Results: After treatment, the improvement of glucose and lipid metabolism indicators and hormone levels in the observation group was significantly better than in the control group (P<0.05). After treatment, the TCM syndrome scores of the two groups were lower than that before treatment (P < 0.001), and the TCM syndrome scores of the observation group was lower than that of the control group (P < 0.001).Ovulation and pregnancy rates were significantly higher in the observation group compared to the control group at 1-year follow up (P<0.05), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05). Conclusions: Combined with conventional drug treatment, TCM nutrition treatment can significantly improve glucose and lipid metabolism, hormone levels, and TCM syndrome of overweight PCOS patients, increase the ovulation and pregnancy rates, and reduce potential adverse reactions.
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BACKGROUND: Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. METHODS: In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). RESULTS: From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1-5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6-52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8-8.2) months, and the median overall survival was 24.5 (95%CI: 10.2-38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. CONCLUSIONS: Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018).
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Antineoplásicos , Hipertensão , Neoplasias de Mama Triplo Negativas , Humanos , Etoposídeo/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Hipertensão/induzido quimicamenteRESUMO
Objectives: To investigate Gegen Qinlian Decoction (GQD) combined with metformin for treatment of patients with Type-2 Diabetes Mellitus (T2DM). Methods: This retrospective observational study reviewed the clinical data of 89 patients diagnosed with T2DM in the Department of Acupuncture and Massage, Hainan Medical University from January 2021 to June 2022. Patients were non-randomized and divided into two groups based on the treatment received: observation group (n=41, GQD combined with metformin); control group (n=48, metformin only). Fasting blood glucose levels (FBG), traditional Chinese medicine (TCM) syndrome scores, clinical effect, blood glucose time in range and adverse reactions were compared between the two groups. Results: There were no statistically significant differences in age, gender, BMI and duration of T2DM between the two groups (P>0.05). The FBG, 2h glucose, HbA1c levels and TCM syndrome scores of the two groups were significantly lower post-treatment (P<0.001) with a greater decrease in the observation group (P<0.001). The observation group was more clinically efficacious than the control group post-treatment (92.68% vs. 77.08%; P<0.05). Blood glucose time in range and the incidence of adverse reactions were lower in the observation group than the control group (P<0.001 and P<0.05). Conclusions: GQD combined with metformin can significantly reduce FBG, 2h glucose and HbA1c levels, and improve TCM syndrome, with good clinical efficacy, shorter blood glucose time in range and less adverse reactions.
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Objective To explore the interaction between abnormal prepregnancy body mass index(pBMI)and high blood lipid level during pregnancy on the risk of gestational diabetes mellitus(GDM). Methods A total of 235 patients with GDM and no blood lipid-related diseases before pregnancy were selected from Hangzhou Women's Hospital during March 2017 to July 2018 as the GDM group.At a ratio of 1â¶3,a total of 705 individual age-matched pregnant women with normal glucose metabolism during prenatal examination from the same hospital were selected as the control group.The generalized multifactor dimension reduction(GMDR)method was employed to characterize the possible interaction between pBMI-blood lipid and GDM.The cross-validation consistency,equilibrium test accuracy,and P value were calculated to evaluate the interaction of each model. Results GMDR model analysis showed that the second-order model including pBMI and gestational blood lipid level had the best performance(P=0.001),with the cross-validation consistency of 10/10 and the equilibrium test accuracy of 64.48%,suggesting that there was a potential interaction between pBMI and gestational high blood lipid level.After adjustment of confounding factors,the model demonstrated that overweight/obesity patients with high triglyceride(TG) level had the highest risk of developing GDM(OR=14.349,95%CI=6.449-31.924,P<0.001).Stratified analysis showed that overweight/obesity patients under high TG level group had a higher risk of developing GDM than normal weight individuals(OR=2.243,95%CI=1.173-4.290,P=0.015). Conclusions Abnormal pBMI and high blood lipid level during pregnancy are the risk factors of GDM and have an interaction between each other.Overweight/obese pregnant women with high TG levels are more likely to develop GDM.
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Diabetes Gestacional , Hiperlipidemias , Índice de Massa Corporal , Feminino , Humanos , Hiperlipidemias/complicações , Obesidade/complicações , Sobrepeso , GravidezRESUMO
In recent years, the incidence of PCa in China has been increasing year by year. Early diagnosis of the malignancy and monitoring of its progression are keys to the reduction of mortality. Currently, early diagnosis of PCa is mainly achieved by determining the level of PSA. Due to the insufficient specificity of PSA, definite diagnosis necessitates needle biopsy, which, as an invasive procedure, causes injury to the patients. Therefore biomarkers seem to be a significant option for the improvement of diagnostic accuracy. Exosomes are 30ï¼150 nm extracellular vesicles secreted by various types of cells in normal and pathological conditions and exist stably in circumcision. Studies show that exosomes contain miRNAs and proteins critical to the progression and metastasis of PCa and have a great potential in the diagnosis of the malignancy. This review outlines the advances in the application of exosomes as novel biomarkers in the diagnosis of PCa.
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Exossomos , MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Próstata/patologiaRESUMO
The effect of stress on male fertility is a widespread public health issue, but less is known about the related signaling pathway. To investigate this, we established a hypercortisolism mouse model by supplementing the drinking water with corticosterone for four weeks. In the hypercortisolism mice, the serum corticosterone was much higher than in the control, and serum testosterone was significantly decreased. Moreover, corticosterone treatment induced decrease of sperm counts and increase of teratozoospermia. Increased numbers of multinucleated giant cells and apoptotic germ cells as well as downregulated meiotic markers suggested that corticosterone induced impaired spermatogenesis. Further, upregulation of macrophage-specific marker antigen F4/80 as well as inflammation-related genes suggested that corticosterone induced inflammation in the testis. Lactate content was found to be decreased in the testis and Sertoli cells after corticosterone treatment, and lactate metabolism-related genes were downregulated. In vitro phagocytosis assays showed that the phagocytic activity in corticosterone-treated Sertoli cells was downregulated and accompanied by decreased mitochondrial membrane potential, while pyruvate dehydrogenase kinase-4 inhibitor supplementation restored this process. Taken together, our results demonstrated that dysfunctional phagocytosis capacity and lactate metabolism in Sertoli cells participates in corticosterone-induced impairment of spermatogenesis.
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Glucocorticoides/toxicidade , Células de Sertoli/fisiologia , Espermatogênese/efeitos dos fármacos , Animais , Proteínas de Ligação ao Cálcio/análise , Corticosterona/toxicidade , Síndrome de Cushing/sangue , Síndrome de Cushing/induzido quimicamente , Síndrome de Cushing/fisiopatologia , Ácido Dicloroacético/farmacologia , Hormônio Foliculoestimulante/sangue , Ácido Láctico/metabolismo , Hormônio Luteinizante/sangue , Masculino , Meiose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Orquite/induzido quimicamente , Orquite/metabolismo , Fagocitose/efeitos dos fármacos , Piruvato Desidrogenase Quinase de Transferência de Acetil/antagonistas & inibidores , Receptores Acoplados a Proteínas G/análise , Células de Sertoli/metabolismo , Contagem de Espermatozoides , Espermatozoides/patologia , Testículo/metabolismo , Testosterona/sangueRESUMO
A series of Mg(Ca)Zr-doped acid-base bifunctional mesoporous silica were synthesized to study the impact of the one-step or two-step impregnation method on material structure. The two-step method seems to be a better way to synthesize metal-based functionalized catalyst and their catalytic performance is investigated using deacetalization-Knoevenagel reaction as the probe reaction. The coexisting dual active sites and suitable designing routes endowed highly efficient (Conv. >99.6%, Sel. >99.8%) and robust stability (10 consecutive cycles) of these materials. The present process succeeded in preparing catalysts decorated with acid-base sites by doping acidic and alkali metal species rather than grafting organic groups.
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In our study, we isolated and characterised two new Senecavirus A (SVA) isolates in Sichuan Province, China. Phylogenetic analysis of both the SVA full-length genomes and the VP1 genes revealed that the two new SVA isolates are more closely related to previous Chinese strains and US strains. The most variable isolate, SVV-SC-01, showed a significant difference from previous SVA strains, and it was identified as a recombinant using several algorithms. Study findings indicate that the SVA virus in China is constantly evolving and new SVA variants may have emerged. Hence, we must take effective measures to prevent further spread of SVA. This report provides evidence that SVA infection of pigs has occurred in Sichuan Province, and the results will contribute to our understanding of the genetic characteristics and recombinant events of SVA in China.
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Genoma Viral , Infecções por Picornaviridae/virologia , Picornaviridae , RNA Viral , Doenças dos Suínos/virologia , Suínos/virologia , Animais , China , Filogenia , Picornaviridae/classificação , Picornaviridae/genética , Picornaviridae/isolamento & purificaçãoRESUMO
Degradable metallic stents, most commonly composed of Mg-based alloys, are of interest as an alternative to traditional metallic stents for application in cardiac and peripheral vasculature. Two major design challenges with such stents are control of the corrosion rate and acute presentation of a nonthrombogenic surface to passing blood. In this study, several types of sulfobetaine (SB)-bearing biodegradable polyurethanes were developed and assessed as physical, chemical, and combination-type coatings for a model degradable Mg alloy, AZ31. For physical coatings, poly(ester sulfobetaine)urethane ureas, PESBUUs were synthesized using variable monomers that allowed the incorporation of a varying extent of carboxyl groups. Introduction of the carboxyl groups was associated with faster polymer degradation time. Simple physical coating of PESBUUs reduced macro- and microscopic thrombogenic deposition together with good stability of the coating attachment compared to a control coating of polylactic- co-glycolic acid. For PESBUUs incorporating carboxyl groups (PESBUUs-COOH), these groups could be converted to siloxane groups (PESBUUs-Si), thus creating polymers that could be surface reacted with the oxidized or phytic acid treated AZ31 surface. Chemical (silanization) attachment of these polymers reduced underlying alloy corrosion rates, but following the salination reaction with physical coating most reduced corrosion rates and protected the surface better from the consequences of oxidation occurring under the coating, such as blistering. The application of a multilayered coating approach using a sulfobetaine-based biodegradable elastomer thus offers options for degradable metallic stent design where thromboresistance is desired in combination with a means to control both polymeric coating degradation rates and underlying alloy corrosion rates.
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Our objective was to investigate the effects of different delivery and feeding modes on the gut microbiota composition of early infants with special emphasis on Bifidobacterium and Lactobacillus profiles at species level. 16S rRNA V3-V4 regions, bifidobacterial, and lactobacilli groEL genes from infant feces were sequenced by Illumina MiSeq. Gut microbiota abundance was significantly different, where standard vaginally delivered (SVD) and breast-fed (BF) groups were higher in comparison with caesarean section (CS), milk-powder-fed (MPF), and mixed-fed (MF) groups. The genus unclassified Enterobacteriaceae was dominant, followed by Bifidobacterium, which was highly abundant in SVD and BF groups. The dominant Bifidobacterium species in all groups were B. longum subsp. longum, B. longum subsp. infantis and B. animalis subsp. lactis. B. dentium and the diversity of Bifidobacterium in SVD and BF groups were significantly higher. For Lactobacillus profiles, L. rhamnosus and L. gasseri were dominant among all the groups, while Lactobacillus species in CS and MPF groups were more diverse. Functional predictions showed significant differences between delivery mode and feeding groups, such as phosphotransferase system as well as taurine and hypotaurine metabolism. In early infants with different delivery and feeding methods, gut microbiota-particularly bifidobacteria and lactobacilli communities-showed significant differences, with strong implications for physiological functions.
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Bifidobacterium/fisiologia , Biodiversidade , Microbioma Gastrointestinal , Lactobacillus/fisiologia , Análise por Conglomerados , Análise Discriminante , Feminino , Microbioma Gastrointestinal/genética , Humanos , Lactente , Masculino , Filogenia , Especificidade da EspécieRESUMO
The first synthesis of 2-methyl-6-pentadecyl-Δ1,6-piperideine (1), a major alkaloid of the piperideine chemotype in fire ant venoms, and its analogues, 2-methyl-6-tetradecyl-Δ1,6-piperideine (2) and 2-methyl-6-hexadecyl-Δ1,6-piperideine (3), was achieved by a facile synthetic method starting with glutaric acid (4) and urea (5). Compound 1 showed in vitro antifungal activity against Cryptococcus neoformans and Candida albicans with IC50 values of 6.6 and 12.4 µg/mL, respectively, and antibacterial activity against vancomycin-resistant Enterococcus faecium with an IC50 value of 19.4 µg/mL, while compounds 2 and 3 were less active against these pathogens. All three compounds strongly inhibited the parasites Leishmania donovani promastigotes and Trypanosoma brucei with IC50 values in the range of 5.0-6.7 and 2.7-4.0 µg/mL, respectively.
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Alcaloides , Venenos de Formiga , Anti-Infecciosos , Piperidinas , Alcaloides/síntese química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Venenos de Formiga/síntese química , Venenos de Formiga/química , Venenos de Formiga/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Formigas/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Resistência a Medicamentos , Enterococcus faecium/efeitos dos fármacos , Concentração Inibidora 50 , Leishmania donovani/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piperidinas/síntese química , Piperidinas/química , Piperidinas/isolamento & purificação , Piperidinas/farmacologia , Piperidonas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Vancomicina/farmacologiaRESUMO
Pain is a complex process of electrical signal transmission. Electroacupuncture may adjust the bioelectric state of the tissues in painful sites through electrical characteristic structural units (acupoints), thereby exerting analgesic effect. The treatment of diseases with electroacupuncture results from the interaction between the external electric field and the electrical properties of acupoint tissues. Therefore, the state of biological tissues and the parameters of electroacupuncture all affect the therapeutic effect.
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Eletroacupuntura , Humanos , Manejo da Dor , Dor , Pontos de AcupunturaRESUMO
Due to the intrinsic contradiction of electrical conductivity and Seebeck coefficient in thermoelectric materials, the enhancement for the power factor (PF) is limited. Since the PF decides the output power, strategies to the enhancement of PF are of paramount importance. In this work, Bi2 Te3 /Sb and Bi2 Te3 /W multilayer films are proposed to enhance the thermoelectric properties. Both systems possess extremely high conductivity of ≈5.6 × 105 S m-1 . Moreover, the electrical conductivity and Seebeck coefficient simultaneously increase as temperature rising, showing the overcome of the intrinsic contradiction. This results in ultrahigh PFs of 1785 µWm-1 K-2 for Bi2 Te3 /W and of 1566 µWm-1 K-2 for Bi2 Te3 /Sb at 600 K. Thermal heating of the Bi2 Te3 /Sb multilayer system shows compositional changes with subsequent formation of Bi-Te-Sb phases, Sb-rich Bi-Te precipitates, and cavities. Contrary, the multilayer structure of the Bi2 Te3 /W films is maintained, while Bi2 Te3 grains of high-crystalline quality are confined between the W layers. In addition, bilayer defects in Bi2 Te3 and smaller cavities at the interface to W layers are also observed. Thus, compositional and confinement effects as well as structural defects result in the ultrahigh PF. Overall, this work demonstrates the strategies on how to obtain ultrahigh PFs of commercial Bi2 Te3 material by microstructure engineering using multilayer structures.
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Leber's hereditary optic neuropathy (LHON) is a maternal inherited disorder, primarily due to mitochondrial DNA (mtDNA) mutations. This investigation aimed to assess the pathogenicity of m.3635G>A alteration known to confer susceptibility to LHON. The disruption of electrostatic interactions among S110 of the MT-ND1 and the side chain of E4, along with the carbonyl backbone of M1 in the NDUFA1, was observed in complex I of cybrids with m.3635G>A. This disturbance affected the complex I assembly activity by changing the mitochondrial respiratory chain composition and function. In addition, the affected cybrids exhibited notable deficiencies in complex I activities, including impaired mitochondrial respiration and depolarization of its membrane potential. Apoptosis was also stimulated in the mutant group, as witnessed by the secretion of cytochrome c and activation of PARP, caspase 3, 7, and 9 compared to the control. Furthermore, the mutant group exhibited decreased levels of autophagy protein light chain 3, accumulation of autophagic substrate P62, and impaired PINK1/Parkin-dependent mitophagy. Overall, the current study has confirmed the crucial involvement of the alteration of the m.3635G>A gene in the development of LHON. These findings contribute to a deeper comprehension of the pathophysiological mechanisms underlying LHON, providing a fundamental basis for further research.
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The 2nd China Vaccinology Integrated Innovation & Teaching Development Conference was held in Sun Yat-sen University, Shenzhen, 18-19, November 2023. Over 200 participants in the field of Vaccinology gathered together to address challenges and issues relevant to vaccine education and training courses, research, and public health programs in China. The conference themed "Promoting the Integrated and Innovative Development of Vaccinology through Collective Efforts." The conference was organized by the China Association of Vaccine (CAV) and hosted by Vaccinology Education Professional Committee of CAV, and School of Public Health (Shenzhen), Sun Yat-sen University. Other partners included the Medical Virology Branch of the Chinese Medical Association, the editorial committee of the Chinese Journal of Preventive Medicine, Human Vaccines & Immunotherapeutics, and the People's Medical Publishing House. The 1st conference was held in Hangzhou, in October 2020.
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Vacinas , Vacinologia , Humanos , Educação em Saúde , Instituições Acadêmicas , ChinaRESUMO
Background: The association between dietary zinc intake and epilepsy remains unclear. This study aimed to investigate the relationship between zinc intake from the diet and epilepsy, employing Mendelian randomization (MR) to explore potential causal links between zinc and epilepsy. Methods: The cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2018. Among the 4,434 participants included, 1.5% (67/4,434) reported having epilepsy. Restricted cubic spline models and logistic regression models were employed to examine the relationships between dietary zinc intakes and epilepsy. Subsequently, a 2-sample Mendelian randomization (MR) analysis was conducted using the inverse variance weighted (IVW) approach as the primary analysis. Results: In the restricted cubic spline (RCS) analysis, the relationship between dietary zinc consumption and epilepsy displayed an L-shaped curve (nonlinear, p = 0.049). After multivariate adjustments, the adjusted odds ratios for epilepsy in T2 (5.0-11.0 mg/day) and T3 (≥11.0 mg/day) were 0.49 (95% confidence interval [CI]: 0.26-0.92, p = 0.026) and 0.60 (95% CI: 0.31-1.17, p = 0.132), respectively, compared to the lowest dietary zinc consumption tertile (T1, ≤5.0 mg/day). The IVW method indicated that genetically predicted zinc intake per standard-deviation increase was inversely associated with three types of epilepsy, including all types of epilepsy (OR = 1.06, 95% CI: 1.02-1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01-1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00-1.02, p = 0.025). Conclusion: Our findings suggest that a daily zinc intake ranging from 5.0 to 11.0 mg is associated with the lowest risk of epilepsy. Furthermore, Mendelian randomization (MR) studies provide additional support for the existence of a causal relationship between zinc and epilepsy.
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Background: Previous studies suggest a link between diet-derived circulating antioxidants and epilepsy, but the causal relationship is unclear. This study aims to investigate the causal effect of these antioxidants on epilepsy. Methods: To assess the causal link between dietary antioxidants and epilepsy risk, we conducted a two-sample Mendelian randomization (MR) analysis. This involved examining antioxidants such as zinc, selenium, α- and γ-tocopherol, vitamin A (retinol), vitamin C (ascorbate), and vitamin E (α-tocopherol). We utilized instrumental variables (IVs) which were genetic variations highly associated with these commonly used antioxidants. Exposure data were sourced from a comprehensive genome-wide association study (GWAS). We aggregated data from the International League Against Epilepsy (ILAE) Consortium sample, which included various types of epilepsy, as an outcome variable. Finally, we applied the inverse variance weighting method and conducted sensitivity analyses for further validation. Results: Based on the primary MR estimates and subsequent sensitivity analyses, the inverse variance weighting (IVW) method revealed that a genetically predicted increase in zinc per standard deviation was positively associated with three types of epilepsy. This includes all types of epilepsy (OR = 1.06, 95% CI: 1.02-1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01-1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00-1.02, p = 0.025). However, there is no evidence indicating that other antioxidants obtained from the diet affect the increase of epilepsy either positively or negatively. Conclusion: Our research indicates that the risk of developing epilepsy may be directly linked to the genetic prediction of zinc, whereas no such association was found for other antioxidants.