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1.
Int J Immunopathol Pharmacol ; 38: 3946320241246713, 2024.
Article in English | MEDLINE | ID: mdl-38649141

ABSTRACT

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.


Subject(s)
Asthma , Nitric Oxide , Obesity , Overweight , Humans , Asthma/physiopathology , Asthma/metabolism , Asthma/diagnosis , Aged , Male , Female , Retrospective Studies , Obesity/physiopathology , Obesity/metabolism , Overweight/physiopathology , Overweight/metabolism , Nitric Oxide/metabolism , Nitric Oxide/analysis , Respiratory Function Tests , Fractional Exhaled Nitric Oxide Testing , China/epidemiology , Bronchial Provocation Tests , Body Mass Index , Asian People , Respiratory Hypersensitivity/physiopathology , Respiratory Hypersensitivity/metabolism , Respiratory Hypersensitivity/diagnosis , Breath Tests
2.
Cancer Chemother Pharmacol ; 93(3): 203-213, 2024 03.
Article in English | MEDLINE | ID: mdl-38141074

ABSTRACT

PURPOSE: Cervical cancer (CC) ranks as the fourth most prevalent malignancy among women worldwide, necessitating effective therapeutic interventions to mitigate its detrimental impact on both physical and mental health. Parthenolide (PTL), a natural product of the sesquiterpene lactone derived from Feverfew leaves, has exhibited promising anti-tumor properties in previous studies; however, its precise effects and underlying molecular mechanisms in CC remain elusive. METHODS: In this work, we investigated the effect of PTL on the proliferation and migration of CC cells. Western blot analysis and Reverse transcription­quantitative PCR were used for mechanistic elucidation. RESULTS: Our findings indicated that PTL substantially inhibited the proliferation of HeLa and SiHa CC cell lines in a dose- and time-dependent manner. Moreover, PTL significantly suppressed the migration of CC cells by down-regulating the expression of vascular endothelial growth factor (VEGF), metastasis-associated protein 1 (MTA1), and transforming growth factor-ß1 (TGF-ß1). Mechanistically, PTL blocked the phosphorylation of focal adhesion kinase (FAK) and glycogen synthase kinase-3ß (GSK3ß) induced by epidermal growth factor (EGF). Further investigations revealed that PTL suppressed the proliferation of CC cells by inhibiting the EGF-mediated phosphorylation of the FAK/GSK3ß signaling pathway. CONCLUSION: Taken together, the present in vitro results suggest that PTL may inhibit the proliferation and migration of CC cells through down-regulating the FAK/GSK3ß signaling pathway, providing new insights for the application of PTL in the treatment of CC.


Subject(s)
Sesquiterpenes , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/drug therapy , Cell Line, Tumor , Glycogen Synthase Kinase 3 beta , Focal Adhesion Protein-Tyrosine Kinases , Epidermal Growth Factor , Vascular Endothelial Growth Factor A , Sesquiterpenes/pharmacology , Cell Proliferation , Cell Movement
3.
Sci Rep ; 13(1): 22511, 2023 12 15.
Article in English | MEDLINE | ID: mdl-38110471

ABSTRACT

G protein-coupled receptors (GPCRs), which regulate numerous intracellular signaling cascades that mediate many essential physiological processes, are attractive yet underexploited insecticide targets. RNA interference (RNAi) technology could facilitate the custom design of environmentally safe pesticides that target GPCRs in select target pests yet are not toxic to non-target species. This study investigates the hypothesis that an RNAi yeast insecticide designed to silence mosquito serotonin receptor 1 (5-HTR1) genes can kill mosquitoes without harming non-target arthropods. 5-HTR.426, a Saccharomyces cerevisiae strain that expresses an shRNA targeting a site specifically conserved in mosquito 5-HTR1 genes, was generated. The yeast can be heat-inactivated and delivered to mosquito larvae as ready-to-use tablets or to adult mosquitoes using attractive targeted sugar baits (ATSBs). The results of laboratory and outdoor semi-field trials demonstrated that consumption of 5-HTR.426 yeast results in highly significant mortality rates in Aedes, Anopheles, and Culex mosquito larvae and adults. Yeast consumption resulted in significant 5-HTR1 silencing and severe neural defects in the mosquito brain but was not found to be toxic to non-target arthropods. These results indicate that RNAi insecticide technology can facilitate selective targeting of GPCRs in intended pests without impacting GPCR activity in non-targeted organisms. In future studies, scaled production of yeast expressing the 5-HTR.426 RNAi insecticide could facilitate field trials to further evaluate this promising new mosquito control intervention.


Subject(s)
Aedes , Insecticides , Animals , RNA Interference , Saccharomyces cerevisiae/genetics , Insecticides/pharmacology , RNA, Small Interfering/genetics , Mosquito Control/methods , Aedes/genetics , Larva/genetics , Receptors, Serotonin, 5-HT1/genetics
4.
Insects ; 14(12)2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38132622

ABSTRACT

Eco-friendly new mosquito control innovations are critical for the ongoing success of global mosquito control programs. In this study, Sh.463_56.10R, a robust RNA interference (RNAi) yeast insecticide strain that is suitable for scaled fermentation, was evaluated under semi-field conditions. Inactivated and dried Sh.463_56.10R yeast induced significant mortality of field strain Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus larvae in semi-field larvicide trials conducted outdoors in St. Augustine, Trinidad, where 100% of the larvae were dead within 24 h. The yeast was also stably suspended in commercial bait and deployed as an active ingredient in miniature attractive targeted sugar bait (ATSB) station sachets. The yeast ATSB induced high levels of Aedes and Culex mosquito morbidity in semi-field trials conducted in Trinidad, West Indies, as well as in Bangkok, Thailand, in which the consumption of the yeast resulted in adult female mosquito death within 48 h, faster than what was observed in laboratory trials. These findings support the pursuit of large-scale field trials to further evaluate the Sh.463_56.10R insecticide, a member of a promising new class of species-specific RNAi insecticides that could help combat insecticide resistance and support effective mosquito control programs worldwide.

5.
Oncol Lett ; 26(6): 519, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37927415

ABSTRACT

Primary liver cancer is one of the most frequently diagnosed malignant tumors seen in clinics, and typically exhibits aggressive invasive behaviors, a poor prognosis, and is associated with high mortality rates. Long-term stress exposure causes norepinephrine (NE) release and activates the ß-Adrenergic receptor (ß-AR), which in turn exacerbates the occurrence and development of different types of cancers; however, the molecular mechanisms of ß-AR in liver cancer are not fully understood. In the present study, reverse transcription (RT)-PCR and RT-quantitative PCR showed that ß-AR expression was upregulated in human liver cancer cells (HepG2) compared with normal liver cells (LO2). Moreover, NE treatment promoted the growth of HepG2 cells, which could be blocked by propranolol, a ß-AR antagonist. Notably, NE had no significant effect on the migration and epithelial-mesenchymal transition in HepG2 cells. Further experiments revealed that NE increased the phosphorylation levels of the extracellular signal-regulated kinase 1/2 (ERK1/2) and cyclic adenosine monophosphate response element-binding protein (CREB), while inhibition of ERK1/2 and CREB activation significantly blocked NE-induced cell proliferation. In summary, the findings of the present study suggested that ß-adrenergic receptor activation promoted the proliferation of HepG2 cells through ERK1/2/CREB signaling pathways.

6.
ACS Appl Mater Interfaces ; 15(35): 41426-41437, 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37612260

ABSTRACT

Nonstoichiometric compounds are widely used in contemporary energy technologies due to their high surface polarity, tailored electronic structure, high electrical conductivity, and other enhanced properties. However, the preparation of such nonstoichiometric compounds can be complicated and, in some cases, uncontrollable and dangerous. Here, we report a "one-pot" strategy for synthesizing N-doped porous graphitic carbon that is hybridized with nonstoichiometric scandium oxide (denoted as ScO0.95@N-PGC) and show that the composite significantly promotes sulfur cathode kinetics in lithium-sulfur (Li-S) batteries. The synthesis of the ScO0.95@N-PGC composite entails heating a porous dry gel that consists of a C source (glucose), a N source (dicyandiamide), and a Sc source (Sc(NO3)3·H2O). Thermally decomposing the dicyandiamide creates a highly reductive atmosphere that simultaneously affords the hypoxic state of the ScO0.95 and dopes the carbon matrix with nitrogen. Density functional theory reveals the presence of oxygen vacancies that enable the ScO0.95 crystals to function as excellent electrical conductors, exhibit enhanced adsorption toward polysulfides, and accelerate the cathode reactions by lowering the corresponding activation energies. Moreover, Li-S cells prepared from the ScO0.95@N-PGC composite display a high specific capacity (1046 mA h g-1 at 0.5 C), an outstanding cycling stability (641 mA h g-1 after 1000 charge-discharge cycles at 0.5 C, a capacity decay of 0.038% per cycle), and a particularly outstanding rate capability (438 mA h g-1 at 8 C). The methodology described establishes a sustainable approach for synthesizing nonstoichiometric compounds while broadening their potential utility in a broad range of energy technologies.

7.
Heliyon ; 9(5): e15924, 2023 May.
Article in English | MEDLINE | ID: mdl-37223713

ABSTRACT

Background: Large cell lung cancer (LCLC) is a rare subtype of non-small cell lung carcinoma (NSCLC), and little is known about its clinical and biological characteristics. Methods: LCLC patient data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. All patients were randomly divided into a training group and a validation group at a ratio of 7:3. The independent prognostic factors that were identified (P < 0.01) by stepwise multivariate Cox analysis were incorporated into an overall survival (OS) prediction nomogram, and risk-stratification systems, C-index, time-ROC, calibration curve, and decision curve analysis (DCA) were applied to evaluate the quality of the model. Results: Nine factors were incorporated into the nomogram: age, sex, race, marital status, 6th AJCC stage, chemotherapy, radiation, surgery and tumor size. The C-index of the predicting OS model in the training dataset and in the test dataset was 0.757 ± 0.006 and 0.764 ± 0.009, respectively. The time-AUCs exceeded 0.8. The DCA curve showed that the nomogram has better clinical value than the TNM staging system. Conclusions: Our study summarized the clinical characteristics and survival probability of LCLC patients, and a visual nomogram was developed to predict the 1-year, 3-year and 5-year OS of LCLC patients. This provides more accurate OS assessments for LCLC patients and helps clinicians make personal management decisions.

8.
Aging (Albany NY) ; 15(7): 2450-2459, 2023 04 01.
Article in English | MEDLINE | ID: mdl-37014329

ABSTRACT

BACKGROUND: Osteosarcoma has become the most common bone malignancy in adolescents. Although the clinical treatment of osteosarcoma has advanced considerably in recent years, the 5-year survival rate has not improved significantly. Recently, many studies have shown that mRNA has unique advantages as a target for drug therapy. Therefore, this study aimed to identify a new prognostic factor and provide a new target for the treatment of osteosarcoma to improve the prognosis of patients. METHODS AND RESULTS: We selected prognostic genes that are closely associated with osteosarcoma clinical features by obtaining osteosarcoma patient information from the GTEx and TARGET databases, and then we developed a risk model. We detected the expression of FKBP11 in osteosarcoma by qRT-PCR, western blotting, and immunohistochemistry and performed CCK-8, Transwell, colony formation, and flow cytometry assays to reveal the regulatory role of FKBP11. We found that FKBP11 was highly expressed in osteosarcoma; silencing FKBP11 expression suppressed the invasion and migration of osteosarcoma cells, slowed cell proliferation, and promoted apoptosis. We also found that silencing the expression of FKBP11 led to inhibition of MEK/ERK phosphorylation. CONCLUSIONS: In conclusion, we validated that the prognostic factor FKBP11 is closely associated with osteosarcoma. Additionally, we identified a novel mechanism by which FKBP11 ameliorates the malignant properties of osteosarcoma cells through the MAPK pathway and serves as a prognostic factor in osteosarcoma. This study provides a new method for the treatment of osteosarcoma.


Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Adolescent , Prognosis , Osteosarcoma/pathology , Cell Proliferation/genetics , Apoptosis/genetics , Bone Neoplasms/pathology , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Tacrolimus Binding Proteins/genetics , Tacrolimus Binding Proteins/metabolism
9.
ACS Appl Mater Interfaces ; 15(9): 11713-11722, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36802456

ABSTRACT

Red phosphorus (RP) is a promising anode material for use in lithium-ion batteries (LIBs) due to its high theoretical specific capacity (2596 mA h g-1). However, the practical use of RP-based anodes has been challenged by the material's low intrinsic electrical conductivity and poor structural stability during lithiation. Here, we describe a phosphorus-doped porous carbon (P-PC) and disclose how the dopant improves the Li storage performance of RP that was incorporated into the P-PC (designated as RP@P-PC). P-doping porous carbon was achieved using an in situ method wherein the heteroatom was added as the porous carbon was being formed. The phosphorus dopant effectively improves the interfacial properties of the carbon matrix as subsequent RP infusion results in high loadings, small particle sizes, and uniform distribution. In half-cells, an RP@P-PC composite was found to exhibit outstanding performance in terms of the ability to store and utilize Li. The device delivered a high specific capacitance and rate capability (1848 and 1111 mA h g-1 at 0.1 and 10.0 A g-1, respectively) as well as excellent cycling stability (1022 mA h g-1 after 800 cycles at 2.0 A g-1). Exceptional performance metrics were also measured when the RP@P-PC was used as an anode material in full cells that contained lithium iron phosphate as the cathode material. The methodology described can be extended to the preparation of other P-doped carbon materials that are employed in contemporary energy storage applications.

10.
Cell Death Dis ; 13(12): 1075, 2022 12 27.
Article in English | MEDLINE | ID: mdl-36575176

ABSTRACT

Nutrient-limiting conditions are common during cancer development. The coordination of cellular glucose levels and cell survival is a fundamental question in cell biology and has not been completely understood. 4EBP1 is known as a translational repressor to regulate cell proliferation and survival by controlling translation initiation, however, whether 4EBP1 could participate in tumor survival by other mechanism except for translational repression function, especially under glucose starvation conditions remains unknown. Here, we found that protein levels of 4EBP1 was up-regulated in the central region of the tumor which always suffered nutrient deprivation compared with the peripheral region. We further discovered that 4EBP1 was dephosphorylated by PTPMT1 under glucose starvation conditions, which prevented 4EBP1 from being targeted for ubiquitin-mediated proteasomal degradation by HERC5. After that, 4EBP1 translocated to cytoplasm and interacted with STAT3 by competing with JAK and ERK, leading to the inactivation of STAT3 in the cytoplasm, resulting in apoptosis under glucose withdrawal conditions. Moreover, 4EBP1 knockdown increased the tumor volume and weight in xenograft models by inhibiting apoptosis in the central region of tumor. These findings highlight a novel mechanism for 4EBP1 as a new cellular glucose sensor in regulating cancer cell death under glucose deprivation conditions, which was different from its classical function as a translational repressor.


Subject(s)
Adaptor Proteins, Signal Transducing , Cell Cycle Proteins , Glucose , Lung Neoplasms , Humans , Cell Death , Cell Proliferation , Glucose/metabolism , Lung Neoplasms/genetics , PTEN Phosphohydrolase/metabolism , Signal Transduction , Animals , Adaptor Proteins, Signal Transducing/metabolism , Cell Cycle Proteins/metabolism
11.
Entropy (Basel) ; 24(11)2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36421532

ABSTRACT

Point cloud data are extensively used in various applications, such as autonomous driving and augmented reality since it can provide both detailed and realistic depictions of 3D scenes or objects. Meanwhile, 3D point clouds generally occupy a large amount of storage space that is a big burden for efficient communication. However, it is difficult to efficiently compress such sparse, disordered, non-uniform and high dimensional data. Therefore, this work proposes a novel deep-learning framework for point cloud geometric compression based on an autoencoder architecture. Specifically, a multi-layer residual module is designed on a sparse convolution-based autoencoders that progressively down-samples the input point clouds and reconstructs the point clouds in a hierarchically way. It effectively constrains the accuracy of the sampling process at the encoder side, which significantly preserves the feature information with a decrease in the data volume. Compared with the state-of-the-art geometry-based point cloud compression (G-PCC) schemes, our approach obtains more than 70-90% BD-Rate gain on an object point cloud dataset and achieves a better point cloud reconstruction quality. Additionally, compared to the state-of-the-art PCGCv2, we achieve an average gain of about 10% in BD-Rate.

13.
Pathogens ; 11(2)2022 Jan 27.
Article in English | MEDLINE | ID: mdl-35215113

ABSTRACT

Although several emerging mosquito control technologies are dependent on mass releases of adult males, methods of sex-sorting that can be implemented globally have not yet been established. RNAi screens led to the discovery of siRNA, which targets gamma-glutamyl transpeptidase (GGT), a gene which is well conserved in multiple species of mosquitoes and located at the sex-determining M locus region in Aedes aegypti. Silencing the A. aegypti, Aedes albopictus, Anopheles gambiae, Culex pipiens, and Culex quinquefasciatus GGT genes resulted in female larval death, with no significant impact on male survival. Generation of yeast strains that permitted affordable expression and oral delivery of shRNA corresponding to mosquito GGT genes facilitated larval target gene silencing and generated significantly increased 5 males:1 female adult ratios in each species. Yeast targeting a conserved sequence in Culex GGT genes was incorporated into a larval mass-rearing diet, permitting the generation of fit adult male C. pipiens and C. quinquefasciatus, two species for which labor-intensive manual sex separation had previously been utilized. The results of this study indicate that female-specific yeast-based RNAi larvicides may facilitate global implementation of population-based control strategies that require releases of sterile or genetically modified adult males, and that yeast RNAi strategies can be utilized in various species of mosquitoes that have progressed to different stages of sex chromosome evolution.

14.
Cold Spring Harb Protoc ; 2022(7): Pdb.prot107808, 2022 07 12.
Article in English | MEDLINE | ID: mdl-35135889

ABSTRACT

RNA interference (RNAi), an innate regulatory mechanism that is conserved across many eukaryotic species, has been harnessed for experimental gene silencing in many organisms, including mosquitoes. This protocol describes an optimized method for inducing RNAi in adult Aedes aegypti and Anopheles gambiae mosquitoes that involves feeding them a red-colored sugar bait containing small interfering RNA (siRNA). This oral delivery method is less physically disruptive than delivery by subcutaneous injection, and the use of siRNAs (in contrast to long dsRNAs) for RNAi enables the design of molecules that target conserved sites so that gene function can be studied in multiple species. After feeding, the behavioral and morbidity phenotypes that result from the suppression of target gene expression can then be analyzed.


Subject(s)
Aedes , Sugars , Aedes/genetics , Animals , Gene Silencing , RNA Interference , RNA, Double-Stranded , RNA, Small Interfering/genetics
15.
Cold Spring Harb Protoc ; 2022(7): Pdb.top107690, 2022 07 12.
Article in English | MEDLINE | ID: mdl-35135890

ABSTRACT

RNA interference (RNAi) has played a key role in the field of insect functional genomics, a discipline that has enhanced the study of developmental, evolutionary, physiological, and molecular biological phenomena in a wide variety of insects, including disease vector mosquitoes. Here we introduce a recently optimized RNAi procedure in which adult mosquitoes are fed with a colored sugar bait containing small interfering RNA (siRNA). This procedure effectively and economically leads to gene silencing, is technically straightforward, and has been successfully used to characterize a number of genes in adult mosquitoes. We also discuss how, in addition to laboratory applications, this oral RNAi procedure might one day be used in the field for controlling insect pests.


Subject(s)
Culicidae , Animals , Culicidae/genetics , Gene Silencing , Insecta/genetics , Mosquito Vectors , RNA Interference , RNA, Double-Stranded , RNA, Small Interfering/genetics
16.
Insects ; 12(11)2021 Nov 02.
Article in English | MEDLINE | ID: mdl-34821787

ABSTRACT

Concerns for widespread insecticide resistance and the unintended impacts of insecticides on nontarget organisms have generated a pressing need for mosquito control innovations. A yeast RNAi-based insecticide that targets a conserved site in mosquito Irx family genes, but which has not yet been identified in the genomes of nontarget organisms, was developed and characterized. Saccharomyces cerevisiae constructed to express short hairpin RNA (shRNA) matching the target site induced significant Aedes aegypti larval death in both lab trials and outdoor semi-field evaluations. The yeast also induced high levels of mortality in adult females, which readily consumed yeast incorporated into an attractive targeted sugar bait (ATSB) during simulated field trials. A conserved requirement for Irx function as a regulator of proneural gene expression was observed in the mosquito brain, suggesting a possible mode of action. The larvicidal and adulticidal properties of the yeast were also verified in Aedes albopictus, Anopheles gambiae, and Culexquinquefasciatus mosquitoes, but the yeast larvicide was not toxic to other nontarget arthropods. These results indicate that further development and evaluation of this technology as an ecofriendly control intervention is warranted, and that ATSBs, an emerging mosquito control paradigm, could potentially be enriched through the use of yeast-based RNAi technology.

17.
Pathogens ; 10(10)2021 Sep 28.
Article in English | MEDLINE | ID: mdl-34684200

ABSTRACT

Prevention of mosquito-borne infectious diseases will require new classes of environmentally safe insecticides and novel mosquito control technologies. Saccharomyces cerevisiae was engineered to express short hairpin RNA (shRNA) corresponding to mosquito Rbfox1 genes. The yeast induced target gene silencing, resulting in larval death that was observed in both laboratory and outdoor semi-field trials conducted on Aedes aegypti. High levels of mortality were also observed during simulated field trials in which adult females consumed yeast delivered through a sugar bait. Mortality correlated with defects in the mosquito brain, in which a role for Rbfox1 as a positive regulator of Notch signaling was identified. The larvicidal and adulticidal activities of the yeast were subsequently confirmed in trials conducted on Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus, yet the yeast had no impact on survival of select non-target arthropods. These studies indicate that yeast RNAi pesticides targeting Rbfox1 could be further developed as broad-based mosquito larvicides and adulticides for deployment in integrated biorational mosquito control programs. These findings also suggest that the species-specificity of attractive targeted sugar baits, a new paradigm for vector control, could potentially be enhanced through RNAi technology, and specifically through the use of yeast-based interfering RNA pesticides.

18.
Pulm Pharmacol Ther ; 70: 102070, 2021 10.
Article in English | MEDLINE | ID: mdl-34403779

ABSTRACT

Copious evidence reveals that long non-coding RNAs (lncRNAs) exert great regulatory functions in various human cancers. LINC01224 is a novel lncRNA, identified as a cancer regulator of HCC. However, the underlying mechanisms and clinical significance of LINC01224 in other types of cancers need further researches to explore. In this study, we aimed to elucidate the biological role of LINC01224 in NSCLC progression. Presently, LINNC01224 expression was elevated and miR-2467 expression was down-regulated in NSCLC, compared with standard control. Then we described the reciprocal correlation between LINC01224 and miR 2467. Afterward, the dual-luciferase reporter assay, RIP assay and RNA pull-down assay validated the base-pair interaction between LINC01224 and miR-2467. Moreover, our findings demonstrated that the silence of LINC01224 inhibited cell proliferation and invasion in NSCLC and enhanced cisplatin (CDDP) sensitivity in vitro. Besides, rescue assays verified that miR-2467 inhibitor could reverse the effects on cell biological activities and CDDP resistance caused by knockdown of LINC01224. Finally, in vivo experiments implicated that knockdown of LINC01224 could inhibit NSCLC tumor growth. To sum up, LINC01224 can promote tumor progression and CDDP resistance in NSCLC via sponging miR-2467, suggesting a promising therapeutic target for better diagnosis and prognosis of NSCLC patients.


Subject(s)
Drug Resistance, Neoplasm , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics
19.
Parasit Vectors ; 14(1): 338, 2021 Jun 26.
Article in English | MEDLINE | ID: mdl-34174948

ABSTRACT

BACKGROUND: Clusters of sex-specific loci are predicted to shape the boundaries of the M/m sex-determination locus of the dengue vector mosquito Aedes aegypti, but the identities of these genes are not known. Identification and characterization of these loci could promote a better understanding of mosquito sex chromosome evolution and lead to the elucidation of new strategies for male mosquito sex separation, a requirement for several emerging mosquito population control strategies that are dependent on the mass rearing and release of male mosquitoes. This investigation revealed that the methylthioribulose-1-phosphate dehydratase (MtnB) gene, which resides adjacent to the M/m locus and encodes an evolutionarily conserved component of the methionine salvage pathway, is required for survival of female larvae. RESULTS: Larval consumption of Saccharomyces cerevisiae (yeast) strains engineered to express interfering RNA corresponding to MtnB resulted in target gene silencing and significant female death, yet had no impact on A. aegypti male survival or fitness. Integration of the yeast larvicides into mass culturing protocols permitted scaled production of fit adult male mosquitoes. Moreover, silencing MtnB orthologs in Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus revealed a conserved female-specific larval requirement for MtnB among different species of mosquitoes. CONCLUSIONS: The results of this investigation, which may have important implications for the study of mosquito sex chromosome evolution, indicate that silencing MtnB can facilitate sex separation in multiple species of disease vector insects.


Subject(s)
Aedes/enzymology , Anopheles/enzymology , Culex/enzymology , Hydro-Lyases/metabolism , Insect Proteins/metabolism , Aedes/genetics , Aedes/growth & development , Animals , Anopheles/genetics , Anopheles/growth & development , Culex/genetics , Culex/growth & development , Female , Hydro-Lyases/genetics , Insect Proteins/genetics , Larva/enzymology , Larva/genetics , Larva/growth & development , Male , Ribulosephosphates/metabolism
20.
J Exp Bot ; 72(15): 5638-5655, 2021 07 28.
Article in English | MEDLINE | ID: mdl-33974693

ABSTRACT

Recent studies have reported that plant-parasitic nematodes facilitate their infection by suppressing plant immunity via effectors, but the inhibitory mechanisms remain poorly understood. This study found that a novel effector MgMO289 is exclusively expressed in the dorsal esophageal gland of Meloidogyne graminicola and is up-regulated at parasitic third-/fourth-stage juveniles. In planta silencing of MgMO289 substantially increased plant resistance to M. graminicola. Moreover, we found that MgMO289 interacts with a new rice copper metallochaperone heavy metal-associated plant protein 04 (OsHPP04), and that rice cytosolic COPPER/ZINC -SUPEROXIDE DISMUTASE 2 (cCu/Zn-SOD2) is the target of OsHPP04. Rice plants overexpressing OsHPP04 or MgMO289 exhibited an increased susceptibility to M. graminicola and a higher Cu/Zn-SOD activity, but lower O2•- content, when compared with wild-type plants. Meanwhile, immune response assays showed that MgMO289 could suppress host innate immunity. These findings reveal a novel pathway for a plant pathogen effector that utilizes the host O2•--scavenging system to eliminate O2•- and suppress plant immunity.


Subject(s)
Oryza , Tylenchoidea , Animals , Copper , Metallochaperones , Oryza/genetics , Plant Diseases
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