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1.
Insect Sci ; 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485691

RESUMEN

The tobacco cutworm Spodoptera litura is one of the most destructive polyphagous crop pests. Olfaction and taste play a crucial role in its host plant selection and sexual communication, but the expression profile of chemosensory genes remains unclear. In this study, we identified 185 chemosensory genes from 7 organs in S. litura by transcriptome sequencing, of which 72 genes were published for the first time, including 27 odorant receptors (ORs), 26 gustatory receptors (GRs), 1 ionotropic receptor (IR), 16 odorant-binding proteins (OBPs), and 2 chemosensory proteins (CSPs). Phylogenetic analyses revealed that ORs, IRs, OBPs, and sensory neuron membrane proteins (SNMPs) were mainly expressed in antennae and sequence-conserved among Noctuidae species. The most differentially expressed genes (DEGs) between sexes were ORs and OBPs, and no DEGs were found in GRs. GR transcripts were enriched in proboscis, and the expression of sugar receptors was the highest. Carbon dioxide receptors, sugar receptor-SliuGR6, and bitter GRs-SlituGR43 and SlituGR66 had higher sequence identities between Noctuidae species. CSPs were broadly expressed in various organs, and SlituCSP13 was a DEG in adult antennae. The functional analysis in the Drosophila OR67d expression system found that SlituOR50, a receptor highly expressed in female antennae, is selectively tuned to farnesyl acetate. The results provide a solid foundation for understanding the molecular mechanisms by which chemosensory genes operate to elicit behavioral responses in polyphagous insects.

3.
J Agric Food Chem ; 71(49): 19408-19421, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38039319

RESUMEN

Olfaction plays an instrumental role in host plant selection by phytophagous insects. Helicoverpa assulta and Helicoverpa armigera are two closely related moth species with different host plant ranges. In this study, we first comparatively analyzed the function of 11 female-biased odorant receptors (ORs) and their orthologs in the two species by the Drosophila T1 neuron expression system and then examined the electroantennography responses of the two species to the most effective OR ligands. Behavioral assays using a Y-tube olfactometer indicate that guaiene, the primary ligand of HassOR21-2 and HarmOR21-2, only attracts the females, while benzyl acetone, the main ligand of HassOR35 and HarmOR35, attracts both sexes of the two species. Oviposition preference experiments further confirm that guaiene and benzyl acetone are potent oviposition attractants for the mated females of both species. These findings deepen our understanding of the olfactory coding mechanisms of host plant selection in herbivorous insects and provide valuable attractants for managing pest populations.


Asunto(s)
Mariposas Nocturnas , Receptores Odorantes , Atractivos Sexuales , Femenino , Animales , Masculino , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Ligandos , Mariposas Nocturnas/metabolismo , Atractivos Sexuales/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo
4.
Phytochemistry ; 209: 113621, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36893826

RESUMEN

The phytochemical investigation of the EtOAc extract from the aerial parts of Isodon eriocalyx afforded seventeen diterpenoids, including eight undescribed compounds. Eriocalyxins H-L have unique structural characteristics featuring a 5-epi-ent-kaurane diterpenoid scaffold with eriocalyxins H-K also possess an unusual 6,11-epoxyspiro-lactone ring while eriocalyxin L, a 1,7:3,20-diepoxy-ent kaurene, features an 1,7-oxygen linkage. The structures of these compounds were elucidated by spectroscopic data interpretation, and the absolute configurations of eriocalyxins H, I, L, and M were confirmed by single-crystal X-ray diffraction. The isolates were screened for their inhibitory activities against VCAM-1 and ICAM-1 at 5 µM. While eriocalyxin O, coetsoidin A and laxiflorin P were found to significantly inhibit both VCAM-1 and ICAM-1, 8 (17),13-ent-labdadien-15 â†’ 16-lactone-19-oic acid displayed evidently inhibitory effect against ICAM-1.


Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Diterpenos , Isodon , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/química , Isodon/química , Molécula 1 de Adhesión Intercelular/análisis , Molécula 1 de Adhesión Celular Vascular/análisis , Antineoplásicos Fitogénicos/química , Diterpenos/química , Componentes Aéreos de las Plantas/química , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales
5.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36614196

RESUMEN

Large numbers of neutrophils infiltrate tumors and comprise a notable component of the inflammatory tumor microenvironment. While it is established that tumor cells exhibit the Warburg effect for energy production, the contribution of the neutrophil metabolic state to tumorigenesis is unknown. Here, we investigated whether neutrophil infiltration and metabolic status promotes tumor progression in an orthotopic mouse model of pancreatic ductal adenocarcinoma (PDAC). We observed a large increase in the proportion of neutrophils in the blood and tumor upon orthotopic transplantation. Intriguingly, these tumor-infiltrating neutrophils up-regulated glycolytic factors and hypoxia-inducible factor 1-alpha (HIF-1α) expression compared to neutrophils from the bone marrow and blood of the same mouse. This enhanced glycolytic signature was also observed in human PDAC tissue samples. Strikingly, neutrophil-specific deletion of HIF-1α (HIF-1αΔNφ) significantly reduced tumor burden and improved overall survival in orthotopic transplanted mice, by converting the pro-tumorigenic neutrophil phenotype to an anti-tumorigenic phenotype. This outcome was associated with elevated reactive oxygen species production and activated natural killer cells and CD8+ cytotoxic T cells compared to littermate control mice. These data suggest a role for HIF-1α in neutrophil metabolism, which could be exploited as a target for metabolic modulation in cancer.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animales , Ratones , Neutrófilos/metabolismo , Línea Celular Tumoral , Ratones Noqueados , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Carcinogénesis , Factor 1 Inducible por Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Microambiente Tumoral/genética , Neoplasias Pancreáticas
6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-969880

RESUMEN

With the determination of the whole genome sequence of varicella-zoster virus (VZV) virus, the successful breakthrough of infectious cloning technology of VZV, and the emergence of effective preventive vaccines, which have been proven to be effective and safe, varicella has become a disease preventable by specific immunity. This article will review the genomic structure, epidemiological characteristics, and research application progress of varicella vaccine and herpes zoster vaccine of varicella zoster virus to provide reference for primary prevention of the disease.


Asunto(s)
Humanos , Herpesvirus Humano 3/genética , Herpes Zóster/prevención & control , Vacuna contra el Herpes Zóster , Vacuna contra la Varicela , Genómica
7.
Proc Natl Acad Sci U S A ; 119(49): e2215442119, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36442117

RESUMEN

Sex pheromones are pivotal for insect reproduction. However, the mechanism of sex pheromone communication remains enigmatic in hymenopteran parasitoids. Here we have identified the sex pheromone and elucidated the olfactory basis of sex pheromone communication in Campoletis chlorideae (Ichneumonidae), a solitary larval endoparasitoid of over 30 lepidopteran pests. Using coupled gas chromatography-electroantennogram detection, we identified two female-derived pheromone components, tetradecanal (14:Ald) and 2-heptadecanone (2-Hep) (1:4.6), eliciting strong antennal responses from males but weak responses from females. We observed that males but not females were attracted to both single components and the blend. The hexane-washed female cadavers failed to arouse males, and replenishing 14:Ald and 2-Hep could partially restore the sexual attraction of males. We further expressed six C. chlorideae male-biased odorant receptors in Drosophila T1 neurons and found that CchlOR18 and CchlOR47 were selectively tuned to 14:Ald and 2-Hep, respectively. To verify the biological significance of this data, we knocked down CchlOR18 and CchlOR47 individually or together in vivo and show that the attraction of C. chlorideae to their respective ligands was abolished. Moreover, the parasitoids defective in either of the receptors were less likely to court and copulate. Finally, we show that the sex pheromone and (Z)-jasmone, a potent female attractant, can synergistically affect behaviors of virgin males and virgin females and ultimately increase the parasitic efficiency of C. chlorideae. Our study provides new insights into the molecular mechanism of sex pheromone communication in C. chlorideae that may permit manipulation of parasitoid behavior for pest control.


Asunto(s)
Receptores Odorantes , Atractivos Sexuales , Masculino , Animales , Insectos , Comunicación , Feromonas , Drosophila
8.
Ying Yong Sheng Tai Xue Bao ; 33(10): 2822-2828, 2022 Oct.
Artículo en Chino | MEDLINE | ID: mdl-36384619

RESUMEN

To understand the synergetic features of economy, society, and ecology in cities, we established an urban ecological-economic-social synergetic index evaluation system from three aspects (per capita green area, per capita GDP, and life expectancy per capita) and created an urban ecological-economic-social synergetic index eva-luation method. We analyzed the synergetic features by comparing the ecological-economic-social synergetic index and comprehensive function scores of 35 typical cities in China. The differences in ecological-economic-social synergy and function score for different city sizes and administrative divisions were investigated, while the synergy level of cities were classified. The results showed that the average ecological-economic-social synergetic index of 35 cities in China was 28.79, with the highest of 3.83 and the lowest of 63.04 in 2016. The synergetic index, urban econo-mic function, and social function were significantly positively correlated with urban population sizes and economic sizes. There were significant differences in synergetic index among cities with different population sizes, economic sizes, and administrative functions. The urbanization in China was still in the status of functional imbalance. Urban development was conducive to improve cities' function, but did not effectively improve the synergy of ecology, economy, and society. The ecological function of cities significantly affected urban synergy, which indicated that the poor urban ecological function was the main restrictive factor for urban synergy in China.


Asunto(s)
Conservación de los Recursos Naturales , Urbanización , China , Ciudades , Ecosistema
9.
PLoS Genet ; 18(10): e1010455, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36206313

RESUMEN

Many plant secondary substances are feeding deterrents for insects and play a key role in the selection of host plants. The taste sensilla of phytophagous insects contain gustatory sensory neurons sensitive to deterrents but the molecular basis of deterrent chemoreception remains unknown. We investigated the function of Gr180, the most highly expressed bitter gustatory receptor in the maxillary galea of Helicoverpa armigera larvae. Functional analyses using the Xenopus oocyte expression system and two-electrode voltage clamp revealed that the oocytes expressing Gr180 responded to coumarin. Tip recording results showed that the medial sensilla styloconica of the maxilla of fifth instar larvae exhibited electrophysiological responses to coumarin. Two-choice feeding bioassays confirmed that coumarin inhibited larval feeding. A homozygous mutant strain of H. armigera with truncated Gr180 proteins (Gr180-/-) was established using the CRISPR-Cas9 system. The responses of the medial sensilla styloconica in Gr180-/- to coumarin were almost abolished, and the responses to sinigrin and strychnine were also significantly decreased. Knockout of Gr180 alleviated the feeding deterrent effects of coumarin, sinigrin, and strychnine. Thus, we conclude that Gr180 is a receptor responding to coumarin,and also participates in sensing sinigrin and strychnine. These results enhance our understanding of the gustatory sensing mechanisms of phytophagous insects to deterrents.


Asunto(s)
Mariposas Nocturnas , Gusto , Animales , Larva/metabolismo , Gusto/genética , Estricnina/metabolismo , Estricnina/farmacología , Maxilar/metabolismo , Mariposas Nocturnas/genética , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Cumarinas/metabolismo , Cumarinas/farmacología
10.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36077444

RESUMEN

The closely related species Helicoverpa armigera (H. armigera) and Helicoverpa assulta (H. assulta) have different host plant ranges and share two principal components of sex pheromones but with reversed ratios. The antennae are the main olfactory organ of insects and play a crucial role in host plant selection and mate seeking. However, the genetic basis for gene expression divergence in the antennae of the two species is unclear. We performed an allele-specific expression (ASE) analysis in the antennal transcriptomes of the two species and their F1 hybrids, examining the connection between gene expression divergence and phenotypic differences. The results show that the proportion of genes classified as all cis was higher than that of all trans in males and reversed in females. The contribution of regulatory patterns to gene expression divergence in males was less than that in females, which explained the functional differentiation of male and female antennae. Among the five groups of F1 hybrids, the fertile males from the cross of H. armigera female and H. assulta male had the lowest proportion of misexpressed genes, and the inferred regulatory patterns were more accurate. By using this group of F1 hybrids, we discovered that cis-related regulations play a crucial role in gene expression divergence of sex pheromone perception-related proteins. These results are helpful for understanding how specific changes in the gene expression of olfactory-related genes can contribute to rapid evolutionary changes in important olfactory traits in closely related moths.


Asunto(s)
Mariposas Nocturnas , Atractivos Sexuales , Animales , Antenas de Artrópodos/metabolismo , Femenino , Masculino , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Atractivos Sexuales/genética , Atractivos Sexuales/metabolismo , Olfato/genética , Transcriptoma
11.
BMC Biol ; 20(1): 214, 2022 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-36175945

RESUMEN

BACKGROUND: Odorant receptors (ORs) as odorant-gated ion channels play a crucial role in insect olfaction. They are formed by a heteromultimeric complex of the odorant receptor co-receptor (Orco) and a ligand-selective Or. Other types of olfactory receptor proteins, such as ionotropic receptors (IRs) and some gustatory receptors (GRs), are also involved in the olfactory system of insects. Orco as an obligatory subunit of ORs is highly conserved, providing an opportunity to systematically evaluate OR-dependent olfactory responses. RESULTS: Herein, we successfully established a homozygous mutant (Orco-/-) of Helicoverpa armigera, a notorious crop pest, using the CRISPR/Cas9 gene editing technique. We then compared the olfactory response characteristics of wild type (WT) and Orco-/- adults and larvae. Orco-/- males were infertile, while Orco-/- females were fertile. The lifespan of Orco-/- females was longer than that of WT females. The expressions of most Ors, Irs, and other olfaction-related genes in adult antennae of Orco-/- moths were not obviously affected, but some of them were up- or down-regulated. In addition, there was no change in the neuroanatomical phenotype of Orco-/- moths at the level of the antennal lobe (including the macroglomerular complex region of the male). Using EAG and SSR techniques, we discovered that electrophysiological responses of Orco-/- moths to sex pheromone components and many host plant odorants were absent. The upwind flight behaviors toward sex pheromones of Orco-/- males were severely reduced in a wind tunnel experiment. The oviposition selectivity of Orco-/- females to the host plant (green pepper) has completely disappeared, and the chemotaxis toward green pepper was also lost in Orco-/- larvae. CONCLUSIONS: Our study indicates that OR-mediated olfaction is essential for pheromone communication, oviposition selection, and larval chemotaxis of H. armigera, suggesting a strategy in which mate searching and host-seeking behaviors of moth pests could be disrupted by inhibiting or silencing Orco expression.


Asunto(s)
Mariposas Nocturnas , Receptores Odorantes , Atractivos Sexuales , Animales , Femenino , Masculino , Electrólitos , Proteínas de Insectos/metabolismo , Canales Iónicos , Larva/genética , Larva/metabolismo , Ligandos , Mariposas Nocturnas/genética , Mutagénesis , Feromonas , Receptores Odorantes/metabolismo , Olfato
12.
J Med Virol ; 94(9): 4193-4205, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35570330

RESUMEN

As one of the most rapidly evolving proteins of the genus Betacoronavirus, open reading frames (ORF8's) function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by reactive oxygen species scavenger and endoplasmic reticulum-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion, we examined the plasma samples of coronavirus disease 2019 (COVID-19) convalescent patients and found that the patients aged from 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in 5-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the human reproductive system.


Asunto(s)
COVID-19 , Infertilidad Masculina , SARS-CoV-2 , Proteínas Virales , Secuencia de Aminoácidos , Animales , Anticuerpos Antivirales/sangre , Fertilidad , Humanos , Infertilidad Masculina/virología , Masculino , Ratones , Sistemas de Lectura Abierta
13.
Pest Manag Sci ; 78(5): 2052-2064, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35124874

RESUMEN

BACKGROUND: The fall armyworm, Spodoptera frugiperda (J. E. Smith), is a polyphagous moth species that is spreading all around the globe. It uses (Z)-9-tetradecenyl acetate (Z9-14:Ac) and (Z)-7-dodecenyl acetate (Z7-12:Ac) (100:3.9) as essential sex pheromone components. However, our understanding of the molecular basis of pheromone detection of S. frugiperda is still incomplete. RESULTS: Herein, we identified six PRs, i.e. SfruOR6, 11, 13, 16, 56, and 62, by transcriptome sequencing. Subsequently, we heterologously expressed them in Drosophila OR67d neurons and determined their response spectra with a large panel of sex pheromones and analogs. Among them, SfruOR13-expressing neurons strongly respond to the major sex pheromone component Z9-14:Ac, but also comparably to (Z,E)-9,12-tetradecadienyl acetate (Z9,E12-14:Ac) and weakly to (Z)-9-dodecenyl acetate (Z9-12:Ac). Both SfruOR56 and SfruOR62 are specifically tuned to the minor sex pheromone component Z7-12:Ac with varying intensities and sensitivities. In addition, SfruOR6 is activated only by Z9,E12-14:Ac, and SfruOR16 by both (Z)-9-tetradecenol (Z9-14:OH) and (Z)-9-tetradecenal (Z9-14:Ald). However, the OR67d neurons expressing SfruOR11 remain silent to all compounds tested, a phenomenon commonly found in the OR11 clade of Noctuidae species. Next, using single sensillum recording, we characterized four sensilla types on the antennae of males, namely A, B, C and D types that are tuned to the ligands of PRs, thereby confirming that S. frugiperda uses both SfruOR56 and SfruOR62 to detect Z7-12:Ac. Finally, using wind tunnel assay, we demonstrate that both Z9,E12-14:Ac and Z9-14:OH act as antagonists to the sex pheromone. CONCLUSION: We have deorphanized five PRs and characterized four types of sensilla responsible for the detection of pheromone compounds, providing insights into the peripheral encoding of sex pheromones in S. frugiperda.


Asunto(s)
Mariposas Nocturnas , Atractivos Sexuales , Animales , Masculino , Feromonas , Receptores de Feromonas/genética , Atractivos Sexuales/farmacología , Spodoptera/genética
14.
Insect Biochem Mol Biol ; 141: 103702, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34942332

RESUMEN

Helicoverpa armigera and H. assulta are sympatric closely related species sharing two sex pheromone components, (Z)-11-hexadecenal (Z11-16:Ald) and (Z)-9-hexadecenal (Z9-16:Ald) but in opposite ratios, 97:3 and 3:97 respectively. This feature makes them a feasible model for studying the evolution of pheromone coding mechanisms of lepidopteran insects. Despite a decade-long study to deorphanize the pheromone receptor (PR) repertoires of the two species, the comparison of the function of all PR orthologs between the two species is incomplete. Moreover, the ligands of OR14 and OR15 have so far not been found, likely due to the missing of the active ligand(s) in the compound panel and/or incompatibility of heterologous expression systems used. In the present study, we expressed the PR repertoires of both Helicoverpa species in Drosophila T1 neurons to comparatively study the function of PRs. Among those PRs, OR13, OR6, and OR14 of both species are functionally conserved and narrowly tuned, and the T1 neurons expressing each of them respond to Z11-16:Ald, (Z)-9-hexadecenol (Z9-16:OH), and (Z)-11-hexadecenyl acetate (Z11-16:Ac), respectively. While HarmOR16-expressing neurons respond strongly to (Z)-9-tetradecenal (Z9-14:Ald) and (Z)-11-hexadecenol (Z11-16:OH), the neurons expressing HassOR16 mainly respond to Z9-14:Ald and also weakly respond to (Z)-9-tetradecenol (Z9-14:OH). Moreover, HarmOR14b-expressing neurons are activated by Z9-14:Ald, whereas HassOR14b-expressing neurons are sensitive to Z9-16:Ald, Z9-14:Ald, and (Z)-9-hexadecenol (Z9-16:OH). In addition, HarmOR15-expressing neurons are selectively responsive to Z9-14:Ald. However, the Drosophila T1 neurons expressing either HarmOR11 or HassOR11 are silent to all of the compounds tested. In summary, except for OR11, we have deorphanized all the PRs of these two Helicoverpa species using a Drosophila expression system and a large panel of pheromone compounds, thereby providing a valuable reference for parsing the code of peripheral coding of pheromones.


Asunto(s)
Proteínas de Insectos/genética , Mariposas Nocturnas/genética , Receptores de Feromonas/genética , Animales , Animales Modificados Genéticamente/genética , Drosophila melanogaster/genética , Proteínas de Insectos/metabolismo , Masculino , Mariposas Nocturnas/metabolismo , Receptores de Feromonas/metabolismo , Especificidad de la Especie
15.
PLoS Genet ; 17(7): e1009527, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34264948

RESUMEN

Glucosinolates are token stimuli in host selection of many crucifer specialist insects, but the underlying molecular basis for host selection in these insects remains enigmatic. Using a combination of behavioral, electrophysiological, and molecular methods, we investigate glucosinolate receptors in the cabbage butterfly Pieris rapae. Sinigrin, as a potent feeding stimulant, elicited activity in larval maxillary lateral sensilla styloconica, as well as in adult medial tarsal sensilla. Two P. rapae gustatory receptor genes PrapGr28 and PrapGr15 were identified with high expression in female tarsi, and the subsequent functional analyses showed that Xenopus oocytes only expressing PrapGr28 had specific responses to sinigrin; when ectopically expressed in Drosophila sugar sensing neurons, PrapGr28 conferred sinigrin sensitivity to these neurons. RNA interference experiments further showed that knockdown of PrapGr28 reduced the sensitivity of adult medial tarsal sensilla to sinigrin. Taken together, we conclude that PrapGr28 is a gustatory receptor tuned to sinigrin in P. rapae, which paves the way for revealing the molecular basis of the relationships between crucifer plants and their specialist insects.


Asunto(s)
Mariposas Diurnas/fisiología , Glucosinolatos , Proteínas de Insectos/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Brassica , Mariposas Diurnas/efectos de los fármacos , Drosophila/genética , Femenino , Regulación de la Expresión Génica , Glucosinolatos/farmacología , Proteínas de Insectos/genética , Larva , Oocitos/metabolismo , Receptores de Superficie Celular/genética , Percepción del Gusto , Xenopus
16.
Drug Dev Res ; 82(8): 1111-1123, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33733518

RESUMEN

CQMUH-011 is a modified adamantane sulfonamide compound, that inhibits macrophage proliferation and possesses anti-inflammatory properties. Here, fresh mouse splenocytes were obtained and stimulated with concanavalin A (ConA, 5 µg/ml) in vitro; and experimental autoimmune hepatitis (AIH) was induced by ConA (20 mg/kg, iv) in vivo, to clarify the protective effects of CQMUH-011 against AIH and its possible mechanisms. Our results demonstrated that CQMUH-011 pretreatment can dose-dependently inhibit the proliferation of splenocytes in vitro. In vivo, CQMUH-011 administration reduced the hepatic histopathological score and the infiltration of lymphocytes in the liver parenchyma; additionally, it downregulated the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in serum, as well as those of methane dicarboxylic aldehyde and myeloperoxidase in the liver tissues. It also down-regulated the expression of p-NF-κB and related proteins in the liver tissues. Furthermore, CQMUH-011 could maintain the balance of CD3+ CD4+ /CD3+ CD8+ and decrease the percentages of CD8+ CD69+ and CD4+ CD25+/- CD69+ T-cells in the splenocytes of ConA-challenged mice. Moreover, we found thatCD4+ CD25+/- CD69+ T-cells were significantly correlated with ALT levels, especially CD4+ CD25- CD69+ T-cells. In conclusion, CQMUH-011 exerts potential protective effects against ConA-induced hepatitis, which may be partially attributed to its inhibition of T cells, especially the suppression of the proliferation of CD4+ CD25- CD69+ and CD8+ CD69+ subsets in the spleen. CQMUH-011 also reduced the early apoptosis of lymphocytes in the thymus.


Asunto(s)
Adamantano , Antiinflamatorios , Hepatitis Autoinmune , Sulfonamidas , Linfocitos T , Animales , Femenino , Ratones , Adamantano/análogos & derivados , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Citocinas/sangre , Centro Germinal/efectos de los fármacos , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/inmunología , Inmunosupresores/farmacología , Activación de Linfocitos/efectos de los fármacos , Ratones Endogámicos BALB C , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología
17.
Insect Biochem Mol Biol ; 131: 103554, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33600999

RESUMEN

Helicoverpa armigera utilizes (Z)-11-hexadecenal (Z11-16:Ald) as its major sex pheromone component. Three pheromone binding proteins (PBPs) and two general odorant binding proteins (GOBPs) are abundantly expressed in the male antennae of H. armigera. However, their precise roles in the olfactory detection of Z11-16:Ald remain enigmatic. To answer this question, we first synthesized the antibody against HarmOR13, an olfactory receptor (OR) primarily responding to Z11-16:Ald and mapped the local associations between PBPs/GOBPs and HarmOR13. Immunostaining showed that HarmPBPs and HarmGOBPs were localized in the supporting cells of trichoid sensilla and basiconic sensilla respectively. In particular, HarmPBP1 and HarmPBP2 were colocalized in the cells surrounding the olfactory receptor neurons (ORNs) expressing HarmOR13. Next, using two noninterfering binary expression tools, we heterologously expressed HarmPBP1, HarmPBP2 and HarmOR13 in Drosophila T1 sensilla to validate the functional interplay between PBPs and HarmOR13. We found that the addition of HarmPBP1 or HarmPBP2, not HarmPBP3, significantly increased HarmOR13's response to Z11-16:Ald. However, the presence of either HarmPBP1 or HarmPBP2 was ineffective to change the tuning breadth of HarmOR13 and modulate the response kinetics of this receptor. Taken together, this work demonstrates both HarmPBP1 and HarmPBP2 are involved in Z11-16:Ald detection. Our results support the idea that PBPs can contribute to the peripheral olfactory sensitivity but do little in modulating the selectivity and the response kinetics of corresponding ORs.


Asunto(s)
Aldehídos/farmacología , Mariposas Nocturnas/metabolismo , Receptores Odorantes/metabolismo , Olfato/fisiología , Animales , Anticuerpos , Antenas de Artrópodos/metabolismo , Inmunohistoquímica/métodos , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/fisiología , Neuronas Receptoras Olfatorias/fisiología , Receptores Odorantes/efectos de los fármacos , Receptores Odorantes/inmunología , Sensilos/metabolismo , Atractivos Sexuales/metabolismo
18.
Clin Microbiol Infect ; 27(4): 576-582, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32553881

RESUMEN

OBJECTIVE: The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. METHODS: Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. RESULTS: A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DISCUSSION: Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02430259.


Asunto(s)
Antituberculosos/farmacología , Isoniazida/farmacología , Rifampin/análogos & derivados , Silicosis/complicaciones , Tuberculosis Pulmonar/prevención & control , Antituberculosos/administración & dosificación , Área Bajo la Curva , China , Esquema de Medicación , Semivida , Humanos , Isoniazida/administración & dosificación , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Rifampin/administración & dosificación , Rifampin/farmacocinética , Rifampin/farmacología , Tuberculosis Pulmonar/complicaciones
19.
Journal of Preventive Medicine ; (12): 135-139, 2021.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-876101

RESUMEN

Objective@#To explore the determinants for health-seeking behavior of the residents after cough for more than 3 weeks in Yiwu, Zhejiang Province, in order to provide reference for prevention and control of respiratory diseases.@*Methods@#A multi-stage cluster random sampling method was used to recruit the community residents aged 5 years and above in Yiwu. A face-to-face questionnaire survey was conducted to collect demographic information, features of cough and health-seeking behaviors in the past month. The multivariate logistic regression model was employed to analyze the associated factors for health-seeking behavior after a cough for more than 3 weeks. @*Results@#Among 6 374 residents investigated, 152 cases had a cough for more than 3 weeks in the past month, accounting for 2.48%. They were( 45.00±21.15 ) years old, including 70 ( 46.05% ) males and 82 ( 53.95% ) females. About 58.55% ( 89 ) of them sought medical treatment. The results of multivariate logistic regression analysis showed that females ( OR=2.100, 95%CI: 1.005-4.391 ), middle school education level ( OR=0.406, 95%CI: 0.168-0.983 ), family annual income of 100 000 to 199 999 yuan ( OR=2.993, 95%CI: 1.215-7.373 ) were associated factors for health-seeking behavior after a cough for more than 3 weeks.@*Conclusion@#The rate of health-seeking behavior after a cough for more than 3 weeks among the residents in Yiwu is 58.55%, which is associated with gender, education level and income.

20.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-909609

RESUMEN

OBJECTIVE Senna and rhubarb are classified as stimulative laxatives, and known to have similar effec?tive constituents, the anthraquinones. Being protected by theβ-glucoside bond, the anthraquinones can reach the intes?tines where they are degraded into complex metabolites by enzymes secreted from the intestinal microbiome. It is these complex metabolites that produce the laxative effects. Then the similarities and differences of action between the anthra?quinones require further elucidation. METHODS Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In the in vitro biotransfor?mation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In the in vivo studies, the same compounds were investigated for purgation induction, with mea?surement of histopathology and multiple aquaporins (Aqps) gene expression in six organs. RESULTS SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regula?tion for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower aquaporin 2 (Aqp2) protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases. CONCLUSION SAQ and RAQ showed similar laxative actions with a similar mechanism, they could display different actions in rat kidneys and livers. We suggest that the clinical usage of senna or rhubarb products should be clarified for patients having chronic kidney or liver diseases.

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