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Increasing evidence has shown that gut microbiota (GM) was involved in the pathophysiology of musculoskeletal disorders through multiple pathways such as protein anabolism, chronic inflammation and immunity, and imbalanced metabolism. We performed a systematic review and meta-analysis of human studies to evaluate GM diversity differences between individuals with and without sarcopenia, and explore bacteria with potential to become biomarkers. PubMed, Embase and Cochrane library were systematically searched from inception to February 16, 2024. Studies were included if they (1) sampled adults with sarcopenia, and (2) performed GM analysis and reported α-diversity, ß-diversity or relative abundance. The methodological quality of included studies and the certainty of evidence were assessed through the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system, respectively. Weighted standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were estimated for α-diversity indices using a fixed-effects and a random-effects model. Beta diversity and the relative abundance of GM were summarized qualitatively. A total of 19 studies involving 6,565 participants were included in this study. Compared with controls, significantly moderate decrease in microbial richness in participants with sarcopenia were found (Chao1: SMD = -0.44; 95%CI, -0.64 to -0.23, I2 = 57.23%, 13 studies; observed species: SMD = -0.68; 95%CI, -1.00 to -0.37, I2 = 66.07%, 5 studies; ACE index: SMD = -0.30; 95%CI, -0.56 to -0.04, I2 = 8.12%, 4 studies), with very low certainty of evidence. Differences in ß-diversity were consistently observed in 84.6% of studies and 97.3% of participants. The detailed analysis of the gut microbial differential abundance identified a loss of Prevotellaceae, Prevotella, and Megamonas in sarcopenia compared with non-sarcopenia. In conclusion, sarcopenia was found to be associated with reduced richness of GM, and supplementing intestinal bacteria described above may contribute to preventing and treating this muscle disease. The research protocol was registered and approved in PROSPERO (CRD42023412849).
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Microbioma Gastrointestinal , Sarcopenia , Sarcopenia/microbiologia , Humanos , Bactérias/classificaçãoRESUMO
AIM: Respiratory sarcopenia (RS) has been newly defined in a position paper by four professional organizations in Japan, and it is necessary to examine its incidence and influencing factors using this new definition. So far, little work has been undertaken; we therefore conducted a longitudinal study to fill this gap. METHODS: Our data were extracted from the China Health and Retirement Longitudinal Study. A total of 4301 older adults with complete data and without RS were chosen in 2011, of whom 3065 were followed up until 2015. The presence of low respiratory muscle strength plus low appendicular skeletal muscles mass was defined as RS based on t. A logistic regression model was used to identify the influencing factors for incident RS. RESULTS: After an average of 4 years of follow-up, the cumulative incidence of RS was 5.2%, and it was particularly high in participants aged >80 (20.9%). Logistic regression analysis showed that being unmarried/divorced/widowed (odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.28-2.66, P = 0.001), not having dyslipidemia (OR = 0.35, 95% CI = 0.19-0.65, P = 0.001), having digestive disease (OR = 1.56, 95% CI = 1.11-2.19, P = 0.010), asthma (OR = 2.77, 95% CI = 1.55-4.94, P = 0.001), edentulism (OR = 1.73, 95% CI = 1.24-2.42, P = 0.001), low handgrip strength (OR = 2.82, 95% CI = 1.99-3.99, P < 0.001), or low 5-m gait speed (OR = 1.92, 95% CI = 1.23-3.01, P = 0.004) were associated with a greater likelihood of developing RS. After further adjustment for age and body mass index, asthma, edentulism, and low handgrip strength remained significant. CONCLUSIONS: The identification and management of older adults with the influencing factors described above could be important in preventing RS. Geriatr Gerontol Int 2024; â¢â¢: â¢â¢-â¢â¢.
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Female mosquitoes produce eggs in gonadotrophic cycles that are divided between a previtellogenic and vitellogenic phase. Previtellogenic females consume water and sugar sources like nectar while also being attracted to hosts for blood feeding. Consumption of a blood meal activates the vitellogenic phase, which produces mature eggs and suppresses host attraction. In this study, we tested the hypothesis that neuropeptide Y-like hormones differentially modulate host attraction behavior in the mosquito Aedes aegypti. A series of experiments collectively indicated that enteroendocrine cells (EECs) in the posterior midgut produce and release neuropeptide F (NPF) into the hemolymph during the previtellogenic phase which stimulates attraction to humans and biting behavior. Consumption of a blood meal, which primarily consists of protein by dry weight, down-regulated NPF in EECs until mature eggs developed, which was associated with a decline in hemolymph titer. NPF depletion depended on protein digestion but was not associated with EEC loss. Other experiments showed that neurons in the terminal ganglion extend axons to the posterior midgut and produce RYamide, which showed evidence of increased secretion into circulation after a blood meal. Injection of RYamide-1 and -2 into previtellogenic females suppressed host attraction, while coinjection of RYamides with or without short NPF-2 also inhibited the host attraction activity of NPF. Overall, our results identify NPF and RYamide as gut-associated hormones in A. aegypti that link host attraction behavior to shifts in diet during sequential gonadotrophic cycles.
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Aedes , Neuropeptídeos , Animais , Aedes/metabolismo , Aedes/fisiologia , Neuropeptídeos/metabolismo , Feminino , Comportamento Alimentar/fisiologia , Hemolinfa/metabolismo , Células Enteroendócrinas/metabolismo , Proteínas de Insetos/metabolismo , Humanos , Vitelogênese/fisiologiaRESUMO
Antimicrobial peptides (AMPs), as immune effectors synthesized by a variety of organisms, not only constitute a robust defense mechanism against a broad spectrum of pathogens in the host but also show promising applications as effective antimicrobial agents. Notably, insects are significant reservoirs of natural AMPs. However, the complex array of variations in types, quantities, antimicrobial activities, and production pathways of AMPs, as well as evolution of AMPs across insect species, presents a significant challenge for immunity system understanding and AMP applications. This review covers insect AMP discoveries, classification, common properties, and mechanisms of action. Additionally, the types, quantities, and activities of immune-related AMPs in each model insect are also summarized. We conducted the first comprehensive investigation into the diversity, distribution, and evolution of 20 types of AMPs in model insects, employing phylogenetic analysis to describe their evolutionary relationships and shed light on conserved and distinctive AMP families. Furthermore, we summarize the regulatory pathways of AMP production through classical signaling pathways and additional pathways associated with Nitric Oxide, insulin-like signaling, and hormones. This review advances our understanding of AMPs as guardians in insect immunity systems and unlocks a gateway to insect AMP resources, facilitating the use of AMPs to address food safety concerns.
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Peptídeos Antimicrobianos , Inocuidade dos Alimentos , Humanos , Animais , Filogenia , Insetos , Óxido NítricoRESUMO
Insects rely on their innate immune system to eliminate pathogenic microbes. As a system component, cytokines transmit intercellular signals to control immune responses. Growth-blocking peptide (GBP) is a member of the stress-responsive peptide family of cytokines found in several orders of insects, including Drosophila. However, the physiological role of GBP in defence against pathogens is not thoroughly understood. In this study, we explored the functions of GBP in a lepidopteran pest, Ostrinia furnacalis. Injection of recombinant O. furnacalis GBP (OfGBP) precursor (proGBP) and chemically synthesised GBP significantly induced the transcription of antimicrobial peptides (AMPs) and other immunity-related genes including immune deficiency (IMD) and Dorsal. The level of OfGBP mRNA was upregulated after bacterial infection. Knockdown of OfGBP expression led to a decrease in IMD, Relish, MyD88 and Dorsal mRNA levels. OfGBP induced phenoloxidase activity and affected hemocyte behaviours in O. furnacalis larvae. In summary, GBP is a potent cytokine, effectively regulating AMP synthesis, melanization response and cellular immunity to eliminate invading pathogens.
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Proteínas de Insetos , Larva , Mariposas , Animais , Mariposas/imunologia , Mariposas/genética , Mariposas/crescimento & desenvolvimento , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Larva/crescimento & desenvolvimento , Larva/imunologia , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/metabolismo , Hemócitos/metabolismo , Imunidade InataRESUMO
Objective@#To investigate sleep quality among patients with hypertension and diabetes, so as to provide the basis for improving the health of patients with chronic diseases.@*Methods@#From May to August 2022, patients with hypertension and diabetes under the community management in 4 counties and cities (districts) of Shaoxing City, Zhejiang Province were recruited using a multi-stage stratified cluster random sampling method. Demographic information, disease history, smoking, alcohol consumption, physical activity and sleep quality were collected by questionnaire surveys, and blood pressure, fasting blood glucose and glycosylated hemoglobin were collected through physical examination and laboratory testing. The incidence of poor sleep quality symptoms (snoring/asphyxia/suffocation, difficulty falling asleep, night awakening, taking sleeping pills and early morning awakening) in patients with diabetes and hypertension was descriptively analyzed, and sleep quality was evaluated.@*Results@#A total of 1 539 patients with hypertension and diabetes were surveyed, including 715 males (46.46%) and 824 females (53.54%). The patients had a mean age of (68.68±7.62) years. The proportions of night awakening, early morning awakening, snoring/asphyxia/suffocation, difficulty falling asleep and taking sleeping pills were 29.82%, 28.53%, 20.73%, 15.79% and 4.29%, respectively. The proportion of poor sleep quality was 66.54%. Employment status, smoking status, moderate/high intensity physical activity and blood pressure control were related to poor sleep quality (all P<0.05).@*Conclusion@#Poor sleep quality is common in patients with hypertension and diabetes, with the main symptoms being night awakening, early morning awakening, difficulty falling asleep and snoring/asphyxia/suffocation.
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Mosquitoes including Aedes aegypti are human disease vectors because females must blood feed to produce and lay eggs. Blood feeding triggers insulin-insulin growth factor signaling (IIS) which regulates several physiological processes required for egg development. A. aegypti encodes 8 insulin-like peptides (ILPs) and one insulin-like receptor (IR) plus ovary ecdysteroidogenic hormone (OEH) that also activates IIS through the OEH receptor (OEHR). In this study, we assessed the expression of A. aegypti ILPs and OEH during a gonadotrophic cycle and produced each that were functionally characterized to further understand their roles in regulating egg formation. All A. aegypti ILPs and OEH were expressed during a gonadotrophic cycle. Five ILPs (1, 3, 4, 7, 8) and OEH were specifically expressed in the head, while antibodies to ILP3 and OEH indicated each was released after blood feeding from ventricular axons that terminate on the anterior midgut. A subset of ILP family members and OEH stimulated nutrient storage in previtellogenic females before blood feeding, whereas most IIS-dependent processes after blood feeding were activated by one or more of the brain-specific ILPs and/or OEH. ILPs and OEH with different biological activities also exhibited differences in IIS as measured by phosphorylation of the IR, phosphoinositide 3-kinase/Akt kinase (AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK). Altogether, our results provide the first results that compare the functional activities of all ILP family members and OEH produced by an insect.
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Aedes , Feminino , Humanos , Animais , Aedes/metabolismo , Ovário/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Mosquitos Vetores , Insulina/metabolismoRESUMO
Background & aims: Evidence regarding the prevalence of pre-treatment sarcopenia and its impact on survival in patients with hematological malignancies (HM) varies across studies. We conducted a systematic review and meta-analysis to summarize this discrepancy. Methods: PubMed, Embase and Cochrane library were systematically searched for relevant studies. Outcomes assessed were: prevalence of pre-treatment sarcopenia, overall survival (OS), progression-free survival (PFS) and complete response (CR). Weighted mean proportion, odds ratios (ORs) and hazard ratios (HRs) were estimated using a fixed-effects and a random-effects model. Results: A total of 27 retrospective cohort studies involving 4,991 patients were included in this study. The prevalence of pre-treatment sarcopenia was 37.0% (95% CI: 32.0%-42.0%) in HM patients <60 years and 51.0% (95% CI: 45.0%-57.0%) in≥60 years. Patients with leukemia had the lowest prevalence, compared with those with other HM (38.0%; 95% CI: 33.0%-43.0%; P = 0.010). The presence of sarcopenia was independently associated with poor OS (HR = 1.57, 95% CI = 1.41-1.75) and PFS (HR = 1.50, 95% CI = 1.22-1.83) throughout treatment period, which may be partially attributed to decreased CR (OR = 0.54, 95% CI = 0.41-0.72), particularly for BMI ≥ 25 (P = 0.020) and males (P = 0.020). Conclusion: Sarcopenia is highly prevalent in patients with HM and an adverse prognostic factor for both survival and treatment efficacy. HM and sarcopenia can aggravate each other. We suggest that in future clinical work, incorporating sarcopenia into risk scores will contribute to guide patient stratification and therapeutic strategy, particularly for the elderly. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42023392550).
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BACKGROUND: The present study aimed to identify individuals with different personalities using latent class analysis and further distinguish those with a high risk of diabetes among different clusters. METHODS: Data were utilized from a large-scale, cross-sectional epidemiological survey conducted in 2018 across 23 provinces in China, employing a multi-stage, stratified sampling technique. Latent class cluster analysis was performed to identify distinct personality clusters based on a series of variables concerning life attitudes. Logistic regression was used to calculate adjusted odds ratios (AORs) after controlling for potential confounding variables, including age, gender, body mass index, smoking status, alcohol consumption, hypertension, and physical activity levels, to determine the association between these groups and diabetes. RESULTS: Four distinct personality clusters were identified, namely the energy-poor (2.0%), self-domination (61.3%), optimistic (21.3%), and irritable (15.4%) groups. The prevalence of diabetes in these groups was 14.6%, 9.7%, 9.3%, and 11.6%, respectively. After adjusting for potential confounders, the "energy-poor group" exhibited more odds of having diabetes as compared to the "optimistic group" (AOR 1.683, 95%CI: 1.052-2.693; P=0.030). CONCLUSION: This study identified an energy-poor group of individuals with a high risk of diabetes. Targeted interventions should consider the emotional and personality characteristics of the elderly.
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Metamaterials have attracted broad attention owing to their unique versatile micro- and nano-structures. As a kind of typical metamaterial, photonic crystals (PhCs) are capable of controlling light propagation and constraining spatial light distribution from the chip level. However, introducing metamaterial into micro-scale light-emitting diodes (µLED) still exists many unknowns to explore. This paper, from the perspective of one-dimensional and two-dimensional PhCs, studies the influence of metamaterials on the light extraction and shaping of µLEDs. The µLEDs with six different kinds of PhCs and the sidewall treatment are analyzed based on finite difference time domain (FDTD) method, in which the optimal match between the PhCs type and the sidewall profile is recommended respectively. The simulation results show that the light extraction efficiency (LEE) of the µLEDs with 1D PhCs increases to 85.3% after optimizing the PhCs, and is further improved to reach 99.8% by the sidewall treatment, which is the highest design record so far. It is also found that the 2D air ring PhCs, as a kind of left-handed metamaterials, can highly concentrate the light distribution into 30° with the LEE of 65.4%, without help of any light shaping device. The surprising light extraction and shaping capability of metamaterials provides a new direction and strategy for the future design and application of µLED devices.
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Matrix metalloproteinases (MMPs) are crucial for tissue remodeling and immune responses in insects, yet it remains unclear how MMPs affect the various immune processes against pathogenic infections and whether the responses vary among insects. In this study, we used the lepidopteran pest Ostrinia furnacalis larvae to address these questions by examining the changes of immune-related gene expression and antimicrobial activity after the knockdown of MMP14 and bacterial infections. We identified MMP14 in O. furnacalis using the rapid amplification of complementary DNA ends (RACE), and found that it was conserved and belonged to the MMP1 subfamily. Our functional investigations revealed that MMP14 is an infection-responsive gene, and its knockdown reduces phenoloxidase (PO) activity and Cecropin expression, while the expressions of Lysozyme, Attacin, Gloverin, and Moricin are enhanced after MMP14 knockdown. Further PO and lysozyme activity determinations showed consistent results with gene expression of these immune-related genes. Finally, the knockdown of MMP14 decreased larvae survival to bacterial infections. Taken together, our data indicate that MMP14 selectively regulates the immune responses, and is required to defend against bacterial infections in O. furnacalis larvae. Conserved MMPs may serve as a potential target for pest control using a combination of double-stranded RNA and bacterial infection.
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Infecções Bacterianas , Mariposas , Animais , Muramidase/genética , Muramidase/metabolismo , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Larva/microbiologia , ImunidadeRESUMO
Compared to other insects, the pea aphid Acyrthosiphon pisum has a reduced immune system with an absence of genes coding for a lot of immunity-related molecules. Notably, nitric oxide synthase (NOS), which catalyses the synthesis of nitric oxide (NO), is present in the pea aphid. However, the role of NO in the immune system of pea aphid remains unclear. In this study, we explored the role of NO in the defence of the pea aphid against bacterial infections and found that the NOS gene of the pea aphid responded to an immune challenge, with the expression of ApNOS observably upregulated after bacterial infections. Knockdown of ApNOS using RNA interference or inhibition of NOS activity increased the number of live bacterial cells in aphids and the mortality of aphids after bacterial infection. Conversely, the increase in NO level in aphids using NO donor inhibited the bacterial growth, increased the survival of bacteria-infected aphids, and upregulated immune genes, such as Toll pathway and phagocytosis related genes. Thus, NO promotes immune responses and plays an important role in the immune system of pea aphid.
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Afídeos , Infecções Bacterianas , Animais , Afídeos/genética , Pisum sativum , Interferência de RNA , Óxido Nítrico Sintase/genética , Infecções Bacterianas/genéticaRESUMO
Anautogenous mosquitoes must blood feed on a vertebrate host to produce eggs. Each gonadotrophic cycle is subdivided into a sugar-feeding previtellogenic phase that produces primary follicles and a blood meal-activated vitellogenic phase in which large numbers of eggs synchronously mature and are laid. Multiple endocrine factors including juvenile hormone (JH), insulin-like peptides (ILPs), ovary ecdysteroidogenic hormone (OEH), and 20-hydroxyecdysone (20E) coordinate each gonadotrophic cycle. Egg formation also requires nutrients from feeding that are stored in the fat body. Regulation of egg formation is best understood in Aedes aegypti but the role different endocrine factors play in regulating nutrient mobilization and storage remains unclear. In this study, we report that adult female Ae. aegypti maintained triacylglycerol (TAG) stores during the previtellogenic phase of the first gonadotrophic cycle while glycogen stores declined. In contrast, TAG and glycogen stores were rapidly mobilized during the vitellogenic phase and then replenishment. Several genes encoding enzymes with functions in TAG and glycogen metabolism were differentially expressed in the fat body, which suggested regulation was mediated in part at the transcriptional level. Gain of function assays indicated that stored nutrients were primarily mobilized by adipokinetic hormone (AKH) while juvenoids and OEH regulated replenishment. ILP3 further showed evidence of negatively regulating certain lipolytic enzymes. Loss of function assays indicated AKH depends on the AKH receptor (AKHR) for function. Altogether, our results indicate that the opposing activities of different hormones regulate nutrient stores during a gonadotrophic cycle in Ae. aegypti.
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Aedes , Feminino , Animais , Aedes/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Ovário/metabolismo , Nutrientes , Glicogênio/metabolismoRESUMO
Objective@#To investigate the clustering of risk factors among populations at high risk of cardiovascular diseases in Shaoxing City, Zhejiang Province, so as to provide the evidence for formulating the cardiovascular disease control measures among populations at high risk of cardiovascular diseases.@*Methods@#The populations with hypertension, diabetes, dyslipidemia and a history of cardio-cerebrovascular disease at ages of 35 to 70 years were sampled from 6 districts (counties) of Shaoxing City using a multi-stage cluster random sampling method from May to July 2021. Participants' demographics, history of disease, smoking, alcohol consumption and drug use were collected through questionnaires, and height, body weight and blood lipid were measured. The participants at high risk of cardiovascular diseases were enrolled, and the prevalence and clustering of five risk factors were investigated, including current smoking, current alcohol consumption, overweight/obesity, never exercise and daily sedentary duration of 3 hours and longer. Factors affecting the clustering of risk factors were identified with an ordinal logistic regression model.@*Results@# Totally 1 695 participants were enrolled, including 940 men (55.46%) and 755 women (44.54%), with a mean age of (62.56±6.08) years old. There were 213 participants with a history of cardio-cerebrovascular disease (12.57%), and the prevalence of hypertension, diabetes and dyslipidemia was 78.53%, 61.95% and 46.78%, respectively, and there were 32.63% of participants with current smoking, 35.99% with current alcohol consumption, 49.38% with overweight/obesity, 62.12% with never exercise and 61.24% with daily sedentary duration of 3 hours and longer, respectively. There were 28.85% of participants with two risk factors, and 46.90% with three to five risk factors. Ordinal logistic regression analysis showed that male (OR=5.430, 95%CI: 4.389-6.726), and development of hypertension (OR=1.655, 95%CI: 1.313-2.090) led to present more numbers of clustering of risk factors, and annual household income of 20 000 to 50 000 Yuan (OR=0.620, 95%CI: 0.473-0.812), a history of cardio-cerebrovascular diseases (OR=0.430, 95%CI: 0.324-0.572), presence of diabetes (OR=0.592, 95%CI: 0.476-0.736) led to less numbers of clustering of risk factors among populations at high risk of cardiovascular diseases. @*Conclusions @#There is clustering of risk factors among populations at high risk of cardiovascular diseases in Shaoxing City. Men, income, history of cardio-cerebrovascular diseases, hypertension and diabetes are factors affecting the clustering of risk factors.
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Myeloid differentiation factor 88 (MyD88) is a pivotal adapter protein involved in activating nuclear factor NF-κB of the Toll pathway in insect innate immunity. MyD88 has been extensively studied in vertebrates and Drosophila. However, the information ascribed to MyD88 in Lepidoptera is scarce. In the present study, an Ostrinia furnacalis MyD88 (OfMyD88) cDNA was cloned and functionally characterized (GenBank accession no. MN906311). The complete cDNA sequence of OfMyD88 is 804 bp, and contains a 630 bp open reading frame encoding 209 amino acid residues. OfMyD88 has the death domain (DD), an intermediate domain, and the Toll/interleukin 1 receptor (TIR) domain. OfMyD88 was widely expressed in immune-related tissues such as hemocytes, fat body, midgut, and integument, with the highest expression level in hemocytes, and the lowest expression level in integument. To clarify the immune function of MyD88, O. furnacalis larvae were challenged with Bacillus thuringiensis (Bt) through feeding. Bt oral infection had significantly up-regulated the expression of OfMyD88 and immune genes, including PPO2 (prophenoloxidase 2), Attacin, Gloverin, Cecropin, Moricin, GRP3 (ß-1, 3-Glucan recognition protein 3), and Lysozyme, and increased the activities of PO and lysozyme in hemolymph of O. furnacalis larvae. Knockdown of OfMyD88 by RNA interference suppressed the expression levels of immune related genes, but not PPO2 in the larvae orally infected with Bt, suggesting that OfMyD88 is involved in defending against Bt invasion through the Toll signaling pathway, but does not affect the PPO expression in O. furnacalis larvae.
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Bacillus thuringiensis , Mariposas , Sequência de Aminoácidos , Animais , Bacillus thuringiensis/genética , DNA Complementar/genética , Larva , Muramidase/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismoRESUMO
Nitric oxide (NO) at a high concentration is an effector to kill pathogens during insect immune responses, it also functions as a second messenger at a low concentration to regulate antimicrobial peptide (AMP) production in insects. Drosophila calcineurin subunit CanA1 is a ubiquitous serine/threonine protein phosphatase involved in NO-induced AMP production. However, it is unclear how NO regulates AMP expression. In this study, we used a lepidopteran pest Ostrinia furnacalis and Drosophila S2 cells to investigate how NO signaling affects the AMP production. Bacterial infections upregulated the transcription of nitric oxide synthase 1/2 (NOS1/2), CanA and AMP genes and increased NO concentration in larval hemolymph. Inhibition of NOS or CanA activity reduced the survival of bacteria-infected O. furnacalis. NO donor increased NO level in plasma and upregulated the production of CanA and certain AMPs. In S2 cells, killed Escherichia coli induced NOS transcription and boosted NO production, whereas knockdown of NOS blocked the NO level increase caused by E. coli. As in O. furnacalis larvae, supplementation of the NO donor increased NO level in the culture medium and AMP expression in S2 cells. Suppression of the key pathway genes showed that the IMD (but not Toll) pathway was involved in the upregulation of CecropinA1, Defensin, Diptericin, and Drosomycin by killed E. coli. Knockdown of NOS also reduced the expression of CanA1 and AMPs induced by E. coli, indicative of a role of NO in the AMP expression. Furthermore, CanA1 RNA interference and inhibition of its phosphatase activity significantly reduced NO-induced AMP expression, and knockdown of IMD suppressed NO-induced AMP expression. Together, these results suggest that NO-induced AMP production is mediated by CanA1 via the IMD pathway.
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Calcineurina , Óxido Nítrico , Monofosfato de Adenosina/metabolismo , Animais , Peptídeos Antimicrobianos , Calcineurina/metabolismo , Drosophila , Escherichia coli/metabolismo , Larva/microbiologia , Óxido Nítrico/metabolismoRESUMO
BACKGROUND: Anautogenous mosquitoes commonly consume nectars and other solutions containing sugar but are thought to only produce eggs in discrete gonadotrophic cycles after blood-feeding on a vertebrate host. However, some anautogenous species are known to produce eggs if amino acids in the form of protein are added to a sugar solution. Unclear is how different sources of amino acids in sugar solutions affect the processes that regulate egg formation and whether responses vary among species. In this study, we addressed these questions by focusing on Aedes aegypti and conducting some comparative assays with Aedes albopictus, Anopheles gambiae, Anopheles stephensi and Culex quinquefasciatus. METHODS: Adult female mosquitoes were fed sugar solutions containing amino acids, peptides or protein. Markers for activation of a gonadotrophic cycle including yolk deposition into oocytes, oviposition, ovary ecdysteroidogenesis, expression of juvenile hormone and 20-hydroxyecdysone-responsive genes, and adult blood-feeding behavior were then measured. RESULTS: The five anautogenous species we studied produced eggs when fed two proteins (bovine serum albumin, hemoglobin) or a mixture of peptides (tryptone) in 10% sucrose but deposited only small amounts of yolk into oocytes when fed amino acids in 10% sucrose. Focusing on Ae. aegypti, cultures were maintained for multiple generations by feeding adult females protein- or tryptone-sugar meals. Ad libitum access to protein- or tryptone-sugar solutions protracted production of ecdysteroids by the ovaries, vitellogenin by the fat body and protease activity by the midgut albeit at levels that were lower than in blood-fed females. Females also exhibited semi-continual oogenesis and repressed host-seeking behavior. CONCLUSIONS: Several anautogenous mosquitoes produce eggs when provided ad libitum access to protein- or peptide-sugar meals, but several aspects of oogenesis also differ from females that blood-feed.
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Aedes , Anopheles , Aedes/fisiologia , Aminoácidos/metabolismo , Animais , Feminino , Oogênese/fisiologia , Peptídeos , Sacarose/metabolismoRESUMO
PURPOSE: To evaluate the impact of BCR-ABL1 transcript type on outcome in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). METHODS: PubMed, Embase and Cochrane library were systematically searched for relevant studies. Outcomes assessed were: major molecular response (MMR) at 6, 12, 18 and 60 months, deep molecular response (DMR) at 6, 12, 18 and 60 months, event-free survival (EFS), progression-free survival (PFS), overall survival (OS) and treatment-free remission (TFR). Odds ratios (ORs) and hazard ratios (HRs) were estimated and pooled using a random effect model. RESULTS: A total of 16 retrospective cohort studies involving 5,411 patients were included in this study. Compared with e13a2 transcripts, there was a statistically significant advantage for patients with e14a2 (alone or with co-expressed e13a2) in terms of MMR and DMR at 6, 12 and 18 months. This benefit was sustained up to 5 years for patients with e14a2 transcripts (OR 1.60, 1.23-2.07 and 2.21, 1.71-2.87, respectively), but not for patients with both transcripts. The expression of e14a2 also improved EFS (HR 0.71, 0.53-0.94) and OS (HR 0.76, 0.57-1.00) throughout treatment period. Importantly, having e14a2 transcripts were associated with a higher rate of TFR (OR 2.94, 1.70-5.08) in CML patients attempting TKI discontinuation. Bayesian network meta-analysis showed that e14a2 had the highest probability to be the most favorable transcript type for all outcomes, followed by both and e13a2. CONCLUSIONS: The expression of e14a2 had a positive impact on MMR, DMR, EFS, OS and TFR. We suggest that in the future, the e14a2 transcript can be added to the list of prognostic factors to guide clinical decisions in treating CML. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/PROSPERO/#myprospero], identifier PROSPERO (CRD42021288440).
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Most mosquito species are anautogenous, which means they must blood feed on a vertebrate host to produce eggs, while a few are autogenous and can produce eggs without blood feeding. Egg formation is best understood in the anautogenous mosquito Aedes aegypti, where insulin-like peptides (ILPs), ovary ecdysteroidogenic hormone (OEH) and 20-hydroxyecdysone (20E) interact to regulate gonadotrophic cycles. Circulating hemocytes also approximately double in abundance in conjunction with a gonadotrophic cycle, but the factors responsible for stimulating this increase remain unclear. Focusing on Ae. aegypti, we determined that hemocyte abundance similarly increased in intact blood-fed females and decapitated blood-fed females that were injected with ILP3, whereas OEH, 20E or heat-killed bacteria had no stimulatory activity. ILP3 upregulated insulin-insulin growth factor signaling in hemocytes, but few genes - including almost no transcripts for immune factors - were differentially expressed. ILP3 also stimulated circulating hemocytes to increase in two other anautogenous (Anopheles gambiae and Culex quinquefasciatus) and two facultatively autogenous mosquitoes (Aedes atropalpus and Culex pipiens molestus), but had no stimulatory activity in the obligately autogenous mosquito Toxorhynchites amboinensis. Altogether, our results identify ILPs as the primary regulators of hemocyte proliferation in association with egg formation, but also suggest this response has been lost in the evolution of obligate autogeny.
Assuntos
Aedes , Culex , Aedes/fisiologia , Animais , Feminino , Hemócitos , Insulina , PeptídeosRESUMO
Macrocentrus cingulum is a principal endoparasite of Ostrinia furnacalis larvae. M. cingulum larvae repress host immune responses for survival and ingest host nutrients for development until emerging. However, most investigations focused on the mechanisms of how wasps repress the host immunity, the triggered immune responses and nutrient status altered by wasps in host are neglected. In this study, we found that parasitized O. furnacalis larvae activated fast recognition responses and produced some effectors such as lysozyme and antimicrobial peptides, along with more consumption of trehalose, glucose, and even lipid to defend against the invading M. cingulum. However, the expression of peroxidase 6 and superoxide dismutase 2 (SOD 2) was upregulated, and the messenger RNA (mRNA) levels of cellular immunity-related genes such as thioester-containing protein 2 (TEP 2) and hemocytin were also reduced, suggesting that some immune responses were selectively shut down by wasp parasitization. Taken together, all the results indicated that parasitized O. furnacalis larvae selectively activate the immune recognition response, and upregulate effector genes, but suppress ROS reaction and cellular immunity, and invest more energy to fuel certain immune responses to defend against the wasp invading. This study provides useful information for further identifying key components of the nutrition and innate immune repertoire which may shape host-parasitoid coevolutionary dynamics.