ABSTRACT
BACKGROUND: Reproductive diapause serves as a valuable strategy enabling insects to survive unfavorable seasonal conditions. However, forcing insects into diapause when the environment is conducive to their well-being can cause them to miss out on seasonal opportunities for reproduction. This outcome not only reduces insect populations but also minimizes crop losses caused by insect feeding. Therefore, altering the timing of diapause initiation presents a potential strategy for managing pests. In this study, we examined the possible role of the Insulin Receptor 1 (InR1) in controlling reproductive diapause entry in the male cabbage beetle, Colaphellus bowringi. RESULTS: Compared to short-day (SD) conditions, long-day (LD) conditions led to reproductive diapause of C. bowringi males, characterized by arrested gonad development, increased Triglyceride (TG) accumulation, and upregulated expression of diapause protein 1 and genes associated with lipogenesis and stress tolerance. Upon employing RNA interference to knock down InR1 under SD conditions, males destined for reproduction were compelled into diapause, evidenced by arrested gonadal development, accumulation of TG, and elevated expression of diapause-related genes. Intriguingly, despite the common association of the absence of juvenile hormone (JH) with reproductive diapause in females, the knockdown of InR1 in males did not significant affect the expression of JH biosynthesis and JH response gene. CONCLUSION: The study highlight InR1 is a key factor involved in regulating male reproductive diapause in C. bowringi. Consequently, targeting insulin signaling could be a viable approach to perturb diapause timing, offering a promising strategy for managing pests with reproductive diapause capabilities. © 2024 Society of Chemical Industry.
Subject(s)
Coleoptera , Diapause, Insect , Receptor, Insulin , Reproduction , Animals , Male , Coleoptera/physiology , Coleoptera/growth & development , Coleoptera/genetics , Receptor, Insulin/metabolism , Receptor, Insulin/genetics , Insect Proteins/metabolism , Insect Proteins/genetics , Photoperiod , FemaleABSTRACT
The use of Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib achieves a remarkable clinical response in mantle cell lymphoma (MCL). Acquired drug resistance, however, is significant and affects long-term survival of MCL patients. Here, we demonstrate that DNA methyltransferase 3A (DNMT3A) is involved in ibrutinib resistance. We find that DNMT3A expression is upregulated upon ibrutinib treatment in ibrutinib-resistant MCL cells. Genetic and pharmacological analyses reveal that DNMT3A mediates ibrutinib resistance independent of its DNA-methylation function. Mechanistically, DNMT3A induces the expression of MYC target genes through interaction with the transcription factors MEF2B and MYC, thus mediating metabolic reprogramming to oxidative phosphorylation (OXPHOS). Targeting DNMT3A with low-dose decitabine inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting DNMT3A-mediated metabolic reprogramming to OXPHOS with decitabine provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory MCL.
Subject(s)
Adenine/analogs & derivatives , Lymphoma, Mantle-Cell , Piperidines , Protein-Tyrosine Kinases , Humans , Animals , Mice , Adult , Agammaglobulinaemia Tyrosine Kinase/metabolism , Drug Resistance, Neoplasm/genetics , DNA Methyltransferase 3A , Oxidative Phosphorylation , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/pathology , Decitabine/metabolism , Decitabine/therapeutic useABSTRACT
Cadmium (Cd) is a toxic heavy metal associated with osteoporosis, liver, and kidney disease. The black soldier fly (BSF) Hermetia illucens may be exposed to Cd during the transformation of livestock manure. The BSF has a high tolerance to Cd. In the previous work of the laboratory, we found that vitamin E (VE) may play a role in the tolerance of BSF to Cd exposure. The main findings are as follows: The BSF larvae pretreated with exogenous VE had heavier body weight, lower content and toxicity of Cd under similar Cd exposure. Even in high Cd exposure at the concentrations of 300 and 700 mg/kg, the BSF larvae pretreated with exogenous VE at a concentration of 100 mg/kg still reduced the Cd toxicity to 85.33 % and 84.43 %, respectively. The best-fitting models showed that metallothionein (MT) content, oxidative damage (8-hydroxydeoxyguanosine content, malondialdehyde content), antioxidant power (total antioxidant power, peroxidase activity) had a great influence on content and toxicity of Cd bioaccumulated in the larvae. The degree of oxidative damage was reduced in the larvae with exogenous VE pretreatments. This variation can be explained by their changed MT content and increased antioxidant power because of exogenous VE. These results reveal the roles of VE in insects defense against Cd exposure and provide a new option for the prevention and therapy of damage caused by Cd exposure.
Subject(s)
Cadmium , Diptera , Animals , Cadmium/toxicity , Vitamin E/pharmacology , Antioxidants , LarvaABSTRACT
The management of diabetic wounds poses a substantial economic and medical burden for diabetic patients. Oxidative stress and persistent bacterial infections are considered to be the primary factors. Qiai essential oil (QEO) exhibits various pharmacological characteristics, including inflammatory-reducing, antibacterial, and antioxidant properties. Nevertheless, the hydrophobic nature and propensity for explosive release of this substance present constraints on its potential for future applications. Here, we developed a stimulus-responsive hydrogel to overcome the multiple limitations of QEO-based wound dressings. The QEO was encapsulated within graphene oxide (GO) through repeated extrusion using an extruder. Subsequently, QEO@GO nanoparticles were incorporated into a Gelatin-methacryloyl (GelMA) hydrogel. The QEO@GO-GelMA hydrogel demonstrated controlled release ablation, photothermal antibacterial effects, and contact ablation against two representative bacterial strains. It effectively reduced reactive oxygen species (ROS) generation, promoted angiogenesis, and decreased levels of the pro-inflammatory cytokine interleukin-6 (IL-6), thereby accelerating the healing process of diabetic wounds. In addition, in vitro and in vivo tests provided further evidence of the favorable biocompatibility of this multifunctional hydrogel dressing. Overall, the QEO@GO-GelMA hydrogel provides numerous benefits, encompassing antimicrobial properties, ROS-scavenging abilities, anti-inflammatory effects, and the capacity to expedite diabetic wound healing. These attributes make it an optimal choice for diabetic wound management.
Subject(s)
Anti-Infective Agents , Diabetes Mellitus , Methacrylates , Humans , Reactive Oxygen Species , Gelatin , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory AgentsABSTRACT
OBJECTIVE: Cardiocerebrovascular disease is a severe threat to human health. Quercetin has a wide range of pharmacological effects such as antitumor and antioxidant. In this study, we aimed to determine how quercetin regulates mitochondrial function in H9c2 cells. METHODS: An H9c2 cell oxygen glucose deprivation/reoxygenation (OGD/R) model was constructed. The expression of miR-92a-3p and mitofusin 1 (Mfn1) mRNA in the cells was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Changes in the mitochondrial membrane potential of cells were examined by JC-1 staining. ATP production in the cells was detected using a biochemical assay. Mitochondrial morphological changes were observed using transmission electron microscopy. Detection of miR-92a-3p binding to Mfn1 was done using dual luciferase. Western blotting was used to detect the protein expression of Mfn1 in the cells. RESULTS: miR-92a-3p is essential in regulating cell viability, apoptosis, and tumor cell metastasis. OGD/R induced miR-92a-3p expression, decreased mitochondrial membrane potential and mitochondrial ATP production, and increased mitochondrial damage. Mitochondria are the most critical site for ATP production. Continued opening of the mitochondrial permeability transition pore results in an abnormal mitochondrial transmembrane potential. Both quercetin and inhibition of miR-29a-3p were able to downregulate miR-29a-3p levels, increase cell viability, mitochondrial membrane potential, and ATP levels, and improve mitochondrial damage morphology. Furthermore, we found that downregulation of miR-29a-3p upregulated the protein expression of Mfn1 in cells. Additionally, miR-92a-3p was found to bind to Mfn1 in a luciferase assay. miR- 29a-3p overexpression significantly inhibited the protein expression level of Mfn1. Quercetin treatment partially reversed the effects of miR-29a-3p overexpression in H9c2 cells. CONCLUSION: Quercetin promoted the recovery of mitochondrial damage in H9c2 cells through the miR-92a-3p/Mfn1 axis.
ABSTRACT
Despite recent advances in the therapy of diffuse large B-cell lymphoma (DLBCL), many patients are still not cured. Therefore, new therapeutic strategies are needed. The anti-apoptotic B-cell lymphoma 2 (BCL2) gene is commonly dysregulated in DLBCL due to various mechanisms such as chromosomal translocation t(14;18)(q32;q21) and copy number alterations; however, targeting BCL-2 with the selective inhibitor, venetoclax, led to response in only a minority of patients. Thus, we sought to identify a rational combination partner of venetoclax to improve its activity against DLBCL cells. Utilizing a functional assay, dynamic BH3 profiling, we found that the DNA hypomethylating agent decitabine increased mitochondrial apoptotic priming and BCL-2 dependence in DLBCL cells. RNA-sequencing analysis revealed that decitabine suppressed the pro-survival PI3K-AKT pathway and altered the mitochondria membrane composition in DLBCL cell lines. Additionally, it induced a DNA damage response and increased BAX and BAK activities. The combination of decitabine and venetoclax synergistically suppressed proliferation of DLBCL cells both in vitro and in vivo in a DLBCL cell line-derived xenograft mouse model. Our study suggests that decitabine plus venetoclax is a promising combination to explore clinically in DLBCL.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Phosphatidylinositol 3-Kinases , Humans , Animals , Mice , Decitabine/pharmacology , Decitabine/therapeutic use , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Proto-Oncogene Proteins c-bcl-2 , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , ApoptosisABSTRACT
Polyethylene glycol (PEG) is widely used as a phase change material (PCM) in thermal energy storage systems due to its high latent heat and chemical stability. However, practical application has been hindered by its low thermal conductivity and leakage issues. Therefore, developing shape-stable high thermal conductivity PCM is of great importance. In this study, new shape-stable composite PCM with high thermal conductivity and leak-prevention capabilities were designed. The porous carbon skeleton of diamond foam (DF) and dual-3D carbon nanotube-diamond foam (CDF) were prepared using the microwave plasma chemical vapor deposition method. The composite materials (DF/PEG and CDF/PEG) were produced by vacuum impregnation with PEG and skeletons. The results showed that CDF/PEG had the highest thermal conductivity, measuring 2.30 W·m-1·K-1, which is 707% higher than that of pure PEG. The employing of 3D networks of CNTs, which can improve the phonon mean free path in DF/PEG (1.79 W·m-1·K-1) while reducing phonon dispersion.The phonon vibration of dual-3D CDF plays an important role in heat transfer. PEG was physically absorbed and well-distributed in CDF, alleviating leakage of liquid PEG. The weight loss of CDF/PEG was only 25% at 70 °C for 120 s. Using CDF is an attractive and efficient strategy to increase the heat transfer of PEG and improve heat storage efficiency, alleviate the problem of poor shape-stability.
ABSTRACT
Objective: To investigate the value of mesenteric CTA combined with D-dimer (DD) level and inflammatory factor changes in evaluating the severity of mesenteric artery embolism. Methods: This is a retrospective study. The imaging data of mesenteric CTA and the levels of plasma DD and inflammatory factors in 120 patients with mesenteric artery embolism confirmed by DSA or surgery in Baoding No.1 Central Hospital were analyzed retrospectively from January 2021 to December 2022. The coincidence rate of CTA alone and CTA combined with DD and inflammatory factors with the results of surgery or DSA was compared and analyzed. The specificity, sensitivity and accuracy of CTA alone and CTA combined with DD and inflammatory factors in diagnosing superior mesenteric artery embolism were compared. The correlations of different severity of mesenteric artery embolism with DD and inflammatory factor levels were compared and analyzed. Results: There was a significant difference in the coincidence rate between CTA diagnosis and CTA combined with DD and inflammatory factors diagnosis (p= 0.01). And the sensitivity and accuracy of the latter were significantly higher than those of the former (sensitivity, p= 0.01; accuracy, p= 0.00). The levels of plasma DD, TNF-a, CRP and IL-6 in the intestinal wall thinning group were significantly higher than those in the thickening group (p= 0.00). The above indexes increased significantly in the decreased intestinal wall enhancement group compared with the increased intestinal wall enhancement group (p= 0.00). DD, TNF-É, CRP and IL-6 levels increased with the increase in stenosis severity. Conclusion: Mesenteric CTA combined with plasma DD and inflammatory factor levels can effectively determine the severity of mesenteric arterial embolism, and provide a scientific basis for early clinical diagnosis and treatment.
ABSTRACT
The B cell leukemia/lymphoma 2 (BCL-2) inhibitor venetoclax is effective in chronic lymphocytic leukemia (CLL); however, resistance may develop over time. Other lymphoid malignancies such as diffuse large B cell lymphoma (DLBCL) are frequently intrinsically resistant to venetoclax. Although genomic resistance mechanisms such as BCL2 mutations have been described, this probably only explains a subset of resistant cases. Using 2 complementary functional precision medicine techniques - BH3 profiling and high-throughput kinase activity mapping - we found that hyperphosphorylation of BCL-2 family proteins, including antiapoptotic myeloid leukemia 1 (MCL-1) and BCL-2 and proapoptotic BCL-2 agonist of cell death (BAD) and BCL-2 associated X, apoptosis regulator (BAX), underlies functional mechanisms of both intrinsic and acquired resistance to venetoclax in CLL and DLBCL. Additionally, we provide evidence that antiapoptotic BCL-2 family protein phosphorylation altered the apoptotic protein interactome, thereby changing the profile of functional dependence on these prosurvival proteins. Targeting BCL-2 family protein phosphorylation with phosphatase-activating drugs rewired these dependencies, thus restoring sensitivity to venetoclax in a panel of venetoclax-resistant lymphoid cell lines, a resistant mouse model, and in paired patient samples before venetoclax treatment and at the time of progression.
Subject(s)
Antineoplastic Agents , Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, Large B-Cell, Diffuse , Mice , Animals , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Drug Resistance, Neoplasm/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , bcl-X Protein/genetics , Apoptosis Regulatory Proteins , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/genetics , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Myeloid Cell Leukemia Sequence 1 Protein/metabolismABSTRACT
BACKGROUND: Acute cerebral infarction is a severe type of ischemic stroke that can be divided into anterior circulation cerebral infarction and posterior circulation cerebral infarction (PCCI). PCCI affects the structure of the posterior circulation brain, because posterior part of the brain, which has more complex anatomical structures and more prone to posterior circulation vascular variation. Therefore, improving the prognosis of PCCI patients is necessary. AIM: To explore the effect of medical care linkage-continuous management mode (MCLMM) on endovascular interventional therapy (EIT) for PCCI. METHODS: Sixty-nine patients with PCCI who received EIT and conventional nursing intervention were selected as the control group, and 78 patients with PCCI who received EIT and MCLMM intervention were selected as the observation group. The incidence of postoperative complications, compliance and disease self-management behavior after six months of intervention, modified Rankin scale (mRS) and Barthel index (BI) scores in the acute phase and after one year of intervention, and recurrence within one year were compared between the two groups. RESULTS: The total incidence rate of postoperative complications in the observation group (7.69%) was lower than that in the control group (18.84%) (P < 0.05). The scores for medical compliance behavior (regular medication, appropriate diet, and rehabilitation cooperation rates) and disease self-management behavior (self-will, disease knowledge, and self-care ability) in the observation group were higher than those in the control group (P < 0.05). After one year of intervention, in the observation group, the mRS score was significantly lower, and the BI score was significantly higher than those in the control group (P < 0.05). The recurrence rate within one year in the observation group (3.85%) was significantly lower than that in the control group (13.04%) (P < 0.05). CONCLUSION: MCLMM can reduce the incidence of complications after EIT for PCCI, improve patient compliance behavior and disease self-management ability, and promote the recovery of neurological function.
ABSTRACT
In recent years, pollution of antibiotics and heavy metal has often been reported in organic wastes. Saprophytic insects have been recorded as biological control agents in organic waste management. During organic waste conversion, the intestinal bacteria of the saprophytic insects play an important role in digestion, physiology, immunity and prevention of pathogen colonization. Black soldier fly (BSF) Hermetia illucens has been widely used as saprophytic insects and showed tolerance to sulfonamides (SAs) and cadmium (Cd). Diversity and changes in gut microbiota of black soldier fly larvae (BSFL) were evaluated through 16S rRNA high-throughput sequencing, and a decrease in diversity of gut microbiota along with an increase in SAs stress was recorded. Major members identified were Actinomycetaceae, Enterobacteriaceae, and Enterococcaceae. And fourteen multi-resistance Klebsiella pneumoniae strains were isolated. Two strains BSFL7-B-5 (from middle midgut of 7-day BSFL) and BSFL11-C-1 (from posterior midgut of 11-day BSFL) were found to be low-toxic and multi-resistance. The adsorption rate of SAs in 5 mg/kg solutions by these two strains reached 65.2% and 61.6%, respectively. Adsorption rate of Cd in 20 mg/L solutions was 77.2% for BSFL7-B-5. The strain BSFL11-C-1 showed higher than 70% adsorption rates of Cd in 20, 30 and 40 mg/L solutions. This study revealed that the presence of multi-resistance bacterial strains in the gut of BSFL helped the larvae against SAs or Cd stress. After determining how and where they are used, selected BSFL gut bacterial strains might be utilized in managing SAs or Cd contamination at suitable concentrations in the future.
Subject(s)
Diptera , Metals, Heavy , Animals , Anti-Bacterial Agents/pharmacology , Bacteria , Biological Control Agents , Cadmium/toxicity , Diptera/microbiology , Klebsiella pneumoniae , Larva , Metals, Heavy/pharmacology , RNA, Ribosomal, 16S/genetics , Sulfanilamide/pharmacology , Sulfonamides/pharmacologyABSTRACT
The mitogen-activated protein kinase (MAPK) signaling pathway is a well-conserved intracellular signal transduction pathway, and has important roles in mammalian reproduction. However, it is unknown whether MAPK also regulates insect reproductive mechanisms. Therefore, we investigated the role of the MAPK signaling pathway in ovarian growth and oviposition in the cabbage beetle Colaphellus bowringi, an economically important pest of Cruciferous vegetables. As an initial step, 14 genes from the extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK (P38) cascades were knocked down using RNA interference (RNAi). The results revealed that RNAi knockdown of MAPK-ERK kinase (MEK), ERK, Kinase suppressor of RAS 2 (KSR2), and P38 induced ovarian development stagnation, low fecundity, and decreased longevity, which indicate that ERK and P38 signaling pathways are important for female C. bowringi survival and reproduction. The potential regulatory role of ERK and P38 pathways in the female reproductive process was investigated using quantitative real-time PCR. We found that ERK pathway possibly regulated ecdysone biosynthesis and P38 pathway possibly involved in the germline stem cell (GSC) development and differentiation. Our findings demonstrated the importance of the MAPK signaling pathway in the female reproduction of insects, and further enhanced the molecular mechanism of female reproductive regulation in insects.
Subject(s)
Brassica , Coleoptera , Animals , Coleoptera/genetics , Female , Mammals/metabolism , Mitogen-Activated Protein Kinases/metabolism , Reproduction , Signal Transduction , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Dihydrosanguinarine (DS) is one of the main chemical constituents of Corydalis bungeana Turcz. which demonstrates anti-inflammatory, antioxidant, and antimicrobial in vitro. The present study aimed to investigate the anti-inflammatory effect and its underlying mechanism of DS in vivo. The network pharmacology method was used to predict the anti-inflammatory target of DS, and it was found that PI3K-AKT signal transduction pathway was the most obvious, and the anti-inflammatory effect of DS was more specific in liver. Herein, we used AKT inhibitor AZD 5363 to block PI3K-AKT signaling pathway, to carry out animal experiments to verify the predicted results of network pharmacology. The results showed that DS exerts protective effects on LPS-induced liver inflammation in mice, and the anti-inflammatory effect of DS was attenuated after inhibiting AKT. To elucidate the potential molecular mechanisms, we performed RNA-sequence analysis in liver tissues. Transcriptome analysis showed that the "TNF signaling pathway" and "IL-17 signaling pathway" had the highest enrichment of differentially expressed genes (DEGs). Then, TNF/IL-17/PI3K-AKT signal pathways were analyzed by GSEA. It was found that AKT3, CCL2, FOS, IL-17A, IL-17RA, IL-17RE, PI3KCA, TRAF3IP2, CREB5, ICAM-1, VCAM-1, IL-1ß, IL-6, TNF-α and CXCL1/2/3 were significantly regulated by DS. The results of RNA-seq immuneCC predictive showed that DS could inhibit the inflammatory response mainly by reducing the degree of macrophage infiltration induced by LPS. At the same time, we use RT-qPCR, IF, WB techniques to verify the core anti-inflammatory differential genes of DS at the gene and protein expression level, confirming that DS can regulate the inflammatory response by regulating the gene expression level of TNF/IL-17/PI3K-AKT signal pathway. We also used HPLC-Q-TOF/MS technology to explore the biotransformation products of DS in the blood and liver of mice under inflammatory conditions and established the docking model of DS and its transformed compound with TNF-α, IL-17A, AKT3 and IL-6, which is the key target from RNA-seq analysis in this study. The results showed that DS strongly interacted with four proteins in the form of prototypes and demethylated products and exhibited anti-inflammatory effects. Our research shows that DS exerts its anti-hepatitis effect mainly by inhibiting the excessive infiltration of macrophages in mice liver induced by LPS and down-regulating the expression of genes related to TNF/IL-17/PI3K-AKT pathway. This study provides a new perspective on the potential therapeutic application of DS and the plasticity of anti-LPS-induced liver inflammation in DS.
Subject(s)
Anti-Inflammatory Agents , Benzophenanthridines , Inflammation , Isoquinolines , Animals , Anti-Inflammatory Agents/pharmacology , Benzophenanthridines/pharmacology , Cytokines/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Interleukin-17/genetics , Interleukin-6/genetics , Isoquinolines/pharmacology , Lipopolysaccharides , Liver/metabolism , Mice , Network Pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA-Seq , Tumor Necrosis Factor-alpha/geneticsABSTRACT
BACKGROUND: The cabbage beetle Colaphellus bowringi is a highly destructive cruciferous vegetable pest in Asia. This beetle is predominantly controlled by synthetic chemical pesticides, which leave pesticide residues on food and constitute a major hidden danger to human health. Based on preliminary research, we hypothesized that the coat protein II (COPII) complex, a primary coated vesicle that exports cargo molecules from the endoplasmic reticulum, is a promising novel target for the control of Colaphellus bowringi. RESULTS: This study investigated whether disrupting COPII using RNA interference (RNAi) affects the growth and development of Colaphellus bowringi adults. The results showed that five COPII assembly genes, Sar1, Sec23, Sec24, Sec13, and Sec31, were uniformly expressed in multiple tissues of adult female Colaphellus bowringi. Injecting double-stranded RNA (dsRNA) against each gene induced a high RNAi efficiency by approximately 55-99%, and considerably inhibited yolk deposition and ovarian growth. Moreover, knockdown of Sar1, Sec23 and Sec24 suppressed feeding and increased mortality to 26.67%, 46.67%, and 42.22%, respectively. This was partially due to the down-regulation of insulin/mTOR-associated nutritional pathways. The results indicate that silencing any of the five genes responsible for COPII complex assembly represses Juvenile hormone and ecdysone signaling pathways, suggesting that vesicle transport plays a vital role in the endocrine regulation of Colaphellus bowringi females. CONCLUSION: This study suggests that the COPII complex could be a promising RNAi target for the management of Colaphellus bowringi, which would reduce our dependence on chemical pesticides for pest control. © 2022 Society of Chemical Industry.
Subject(s)
Brassica , Coleoptera , Pesticides , Animals , Coleoptera/physiology , Female , Juvenile Hormones/metabolism , Pesticides/metabolism , RNA InterferenceABSTRACT
We analyzed, for the first time, the major components and biological properties of the venom of Vespa bicolor, a wasp from South China. Using HPLC and SDS-PAGE, combined with LC-MS/MS, MALDI-TOF-MS, and NMR data to analyze V. bicolor venom (VBV), we found that VBV contains three proteins (hyaluronidase A, phospholipase A1 (two isoforms), and antigen 5 protein) with allergenic activity, two unreported proteins (proteins 5 and 6), and two active substances with large quantities (mastoparan-like peptide 12a (Vb-MLP 12a), and 5-hydroxytryptamine (5-HT)). In addition, the antimicrobial activity of VBV was determined, and results showed that it had a significant effect against anaerobic bacteria. The minimum inhibitory concentration and minimum bactericidal concentration for Propionibacterium acnes were 12.5 µg/mL. Unsurprisingly, VBV had strong antioxidant activity because of the abundance of 5-HT. Contrary to other Vespa venom, VBV showed significant anti-inflammatory activity, even at low concentrations (1 µg/mL), and we found that Vb-MLP 12a showed pro-inflammatory activity by promoting the proliferation of RAW 264.7 cells. Cytotoxicity studies showed that VBV had similar antiproliferative effects against all tested tumor cell lines (HepG2, Hela, MCF-7, A549, and SASJ-1), with HepG2 being the most susceptible. Overall, this study on VBV has high clinical importance and promotes the development of Vespa bicolor resources.
Subject(s)
Insect Proteins , Wasp Venoms , Wasps/chemistry , A549 Cells , Animals , China , HeLa Cells , Hep G2 Cells , Humans , Insect Proteins/chemistry , Insect Proteins/pharmacology , MCF-7 Cells , Microbial Sensitivity Tests , Wasp Venoms/chemistry , Wasp Venoms/pharmacologyABSTRACT
Lead (Pb) is a typical toxic contamination source all over the world. In this research, larvae of the housefly (Musca domestica) were fed a Pb-contaminated diet at different Pb doses of 0, 20 and 5000 mg/kg. RNA sequencing was used to identify genes that were differentially expressed in relation to lead transport or detoxification. RNA interference (RNAi) was carried on 12 candidate genes. The results showed that three luminal pH regions of mid-gut were at pH values of 6.33, 3.10, and 7.80. With increasing Pb concentration, the pH of the middle mid-gut decreased by one unit. The expression levels of carboxypeptidase A (CPA1), glutathione S-transferase (GST), and cytochrome b (Cyt b) were linked to Pb treatments, particularly high Pb concentration of 5000 mg/kg. RNAi-mediated down expression of CPA1, GST2, and CYTb-c1 resulted in low Pb accumulation in the larvae of 5000 mg/kg Pb group. These proteins played key roles in Pb transport and detoxification in M. domestica larvae.
ABSTRACT
Background: Post-stroke depression (PSD) can aggravate the mortality and recurrence rate in stroke patients. The relationship between family functioning and PSD at different phases after a first-ever stroke is unclear. The purpose of this longitudinal study was to investigate the patterns and relationship of family functioning and PSD at acute hospitalization and 6 months post-discharge in first-ever stroke survivors. Methods: This is a longitudinal study conducted in Guangzhou, China. Family functioning and depression were measured by the Short Form Family Assessment Device (SF-FAD) and Self-Rating Depression Scale (SDS) at baseline and 6 months post-discharge. Multiple linear regression analysis was used to explore the relationship between family functioning and PSD. Results: The prevalence of PSD at acute hospitalization and 6 months post-discharge was 32.9% and 20.0%, respectively. SDS scores decreased significantly from baseline to 6 months post-discharge, while SF-FAD scores did not change significantly during this period. The Pearson correlation coefficient showed that SF-FAD scores were positively associated with SDS scores at the two time points (r 1 = 0.341, r 2 = 0.510, P < 0.05). Multiple linear regression analyses indicated that SF-FAD scores could predict PSD at baseline (unstandardized coefficient: 7.010, P < 0.05) and 6 months post-discharge (unstandardized coefficient: 9.672, P < 0.001). Conclusion: This study found that first-ever stroke survivors had good family functioning at baseline and 6 months post-discharge. The findings in this study verified that poor family functioning is positively associated with PSD at different phases post-stroke. Good family functioning is an important protective factor against PSD.
ABSTRACT
BACKGROUND: Risk factor management via behavioral change contributes substantially to secondary stroke prevention. The health belief model identified self-perceived risk as a significant factor in behavior change. In previous studies, people have tended to incorrectly estimate their risk of stroke. Little is known about the differences in stroke knowledge and health behaviors in patients who have had a stroke with different risks of stroke recurrence in China. OBJECTIVE: The aims of this study were to determine the accuracy of self-perceived risk of stroke recurrence and to compare stroke knowledge and health behaviors in patients with hypertensive stroke at different recurrence risk strata. METHODS: Baseline data from 174 patients in the Comprehensive Reminder System based on the Health Belief Model (CRS-HBM) study were used. Self-perceived risk was assessed via the susceptibility subcategory of the Short-Form Health Belief Model Scale, and actual risk was stratified using the Essen Stroke Risk Score. RESULTS: Only 27.0% of the patients estimated their risks of stroke recurrence accurately. Patients who perceived themselves to be at higher risk had better knowledge of warning signs. Compared with patients who underestimated their risk of stroke recurrence, those who accurately estimated or overestimated their risk less likely to smoke. CONCLUSIONS: Most patients incorrectly estimated their risk of stroke recurrence. Communicating with patients about their future risk of recurrent stroke may help improve their stroke knowledge and health behaviors. Implementation of the Comprehensive Reminder System based on the Health Belief Model focusing on risk education aimed at prevention of stroke recurrence is warranted in China.
Subject(s)
Hypertension , Stroke , Health Behavior , Health Belief Model , Health Knowledge, Attitudes, Practice , Humans , Hypertension/complications , Reminder Systems , Stroke/complications , Stroke/prevention & controlABSTRACT
Lipids are a critical source of stored energy in insects, and their metabolism is essential for growth, development, and reproduction. Adequate provisioning of lipids and yolk proteins in the oocytes is essential to ensure reproductive output. Therefore, it is particularly important to understand the molecular mechanisms linking lipid metabolism and reproduction. Lipin proteins are emerging as pivotal modulators of lipid metabolism. They exert a dual function as phosphatidate phosphatase enzymes involved in lipid synthesis and as transcriptional coactivators of genes related to lipid metabolism. However, the functional relationship between lipid metabolism and reproduction remains unclear. In this study, the role of lipin protein in the reproduction of female cabbage beetle Colaphellus bowringi was examined. It was found that Lipin was broadly expressed in the tissues of adult females, with relatively high transcript levels in the head, midgut, fat body, malpighian tubules, and epidermis. RNA interference experiments were conducted using double-stranded RNA against Lipin in C. bowringi females. Lipin silencing blocked ovarian development and strongly suppressed transcription of vitellogenin and vitellogenin receptor genes. In addition, the reduction in Lipin expression led to a rapid increase in lipid storage in the fat body and also promoted the expression of genes related to lipid synthesis and stress tolerance. Overall, these results suggest that a Lipin-mediated lipolytic system is essential for maintaining lipid homeostasis during reproduction in C. bowringi. The findings of this study provide a foundation for future studies on the relationship between lipid metabolism and reproduction in invertebrates.
Subject(s)
Coleoptera/physiology , Insect Proteins/metabolism , Lipid Metabolism , Animals , Female , ReproductionABSTRACT
In insects, the juvenile hormone (JH) biosynthetic pathway regulates the in vivo JH titer. Thus, its downregulation potentially contributes to the lowering of JH titers typically observed in insects undergoing reproductive diapause, a developmental arrest at the adult stage. However, no systematic evidence has yet been presented to demonstrate the physiological and genetic roles of JH biosynthetic genes in reproductive diapause. In this work, we performed RNA interference (RNAi)-based reverse genetic analyses by targeting JH biosynthetic genes, followed by analysis of the reproductive diapause traits in Colaphellus bowringi, an economically important cabbage beetle. We identified a total of 22 genes encoding homologues of enzymes involved in the mevalonate pathway and the JH branch of JH biosynthesis in C. bowringi. Among these, 18 genes showed significant downregulation of their expression in the long day-induced diapausing females, compared to the short day-induced reproductive females. RNAi knockdown of almost any one of the 18 genes in reproductive females reduced the expression of the JH-responsive gene, Krüppel homolog1 (Kr-h1), indicating a lowered circulating JH. Most importantly, depleting transcripts of 3-hydroxy-3-methylglutaryl-CoA reductase 2 (HMGR2), farnesyl-pyrophosphate synthase 1 (FPPS1) and juvenile hormone acid methyltransferase 1 (JHAMT1) induced diapause-associated traits, including immature and inactive ovaries, large accumulations of lipids and adult burrowing behavior. Meanwhile, genes related to ovarian development, lipid accumulation and stress response showed expression patterns like those of diapausing females. RNAi-mediated diapause phenotypes could be reversed to reproductive phenotypes by application of methoprene, a JH receptor agonist. These results suggest that photoperiodic reproductive diapause in C. bowringi is triggered by transcriptional suppression of JH biosynthetic genes, with HMGR2, FPPS1 and JHAMT1 playing a critical role in this process. This work provides sufficient evidence to reveal the physiological roles of JH biosynthetic genes in reproductive diapause.