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1.
Oncol Rep ; 51(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38624021

RESUMO

It has been reported that PL2L60 proteins, a product of PIWIL2 gene which might be activated by an intragenic promoter, could mediate a common pathway specifically for tumorigenesis. In the present study, it was further identified by using western blot assay that the PL2L60 proteins could be degraded in cancer cells through a mechanism of selective autophagy in response to oxidative stress. The PL2L60 was downregulated in various types of cancer cells under the hypoxic condition independently of HIF­1α, resulting in apoptosis of cancer cells. Inhibition of autophagy by small interfering RNA targeting of either Beclin­1 (BECN1) or Atg5 resulted in restoration of PL2L60 expression in hypoxic cancer cell. The hypoxic degradation of PL2L60 was also blocked by the attenuation of the autophagosome membrane protein Atg8/microtubule­associated protein 1 light chain 3 (LC3) or autophagy cargo protein p62 expression. Surprisingly, Immunofluorescence analysis demonstrated that LC3 could be directly bound to PL2L60 and was required for the transport of PL2L60 from the nucleus to the cytoplasm for lysosomal flux under basal or activated autophagy in cancer cells. Moreover, flow cytometric analysis displayed that knocking down of PL2L60 mRNA but not PIWIL2 mRNA effectively inhibited cancer cell proliferation and promoted apoptosis of cancer cells. The similar results were obtained from in vivo tumorigenic experiment, in which PL2L60 downregulation in necroptosis areas was confirmed by immunohistochemistry. These results suggested that various cancer could be suppressed by promoting autophagy. The present study revealed a key role of autophagic degradation of PL2L60 in hypoxia­induced cancer cell death, which could be used as a novel therapeutic target of cancer.


Assuntos
Neoplasias , Humanos , RNA Interferente Pequeno/metabolismo , Hipóxia/metabolismo , Apoptose , Autofagia , Estresse Fisiológico , RNA Mensageiro , Proteínas Argonautas/metabolismo
2.
Nat Commun ; 15(1): 1182, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383554

RESUMO

High reproductive compatibility between crops and their wild relatives can provide benefits for crop breeding but also poses risks for agricultural weed evolution. Weedy rice is a feral relative of rice that infests paddies and causes severe crop losses worldwide. In regions of tropical Asia where the wild progenitor of rice occurs, weedy rice could be influenced by hybridization with the wild species. Genomic analysis of this phenomenon has been very limited. Here we use whole genome sequence analyses of 217 wild, weedy and cultivated rice samples to show that wild rice hybridization has contributed substantially to the evolution of Southeast Asian weedy rice, with some strains acquiring weed-adaptive traits through introgression from the wild progenitor. Our study highlights how adaptive introgression from wild species can contribute to agricultural weed evolution, and it provides a case study of parallel evolution of weediness in independently-evolved strains of a weedy crop relative.


Assuntos
Variação Genética , Oryza , Evolução Molecular , Porosidade , Melhoramento Vegetal , Sudeste Asiático , Plantas Daninhas/genética , Oryza/genética
3.
Plant Commun ; 5(4): 100820, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38221758

RESUMO

Invasive alien species are primary drivers of biodiversity loss and species extinction. Smooth cordgrass (Spartina alterniflora) is one of the most aggressive invasive plants in coastal ecosystems around the world. However, the genomic bases and evolutionary mechanisms underlying its invasion success have remained largely unknown. Here, we assembled a chromosome-level reference genome and performed phenotypic and population genomic analyses between native US and introduced Chinese populations. Our phenotypic comparisons showed that introduced Chinese populations have evolved competitive traits, such as early flowering time and greater plant biomass, during secondary introductions along China's coast. Population genomic and transcriptomic inferences revealed distinct evolutionary trajectories of low- and high-latitude Chinese populations. In particular, genetic mixture among different source populations, together with independent natural selection acting on distinct target genes, may have resulted in high genome dynamics of the introduced Chinese populations. Our study provides novel phenotypic and genomic evidence showing how smooth cordgrass rapidly adapts to variable environmental conditions in its introduced ranges. Moreover, candidate genes related to flowering time, fast growth, and stress tolerance (i.e., salinity and submergence) provide valuable genetic resources for future improvement of cereal crops.


Assuntos
Ecossistema , Plantas , Poaceae/genética , Genômica , Espécies Introduzidas
4.
Clin Cosmet Investig Dermatol ; 16: 3267-3278, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021430

RESUMO

Background and Aim: Psoriasis is a persistent inflammatory disorder that affects 3% of the population and is associated with cardiovascular diseases. Therefore, this study aimed to investigate the correlations between complete blood cell count (CBC)-derived inflammatory biomarkers, psoriasis prevalence, and all-cause mortality. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2006 and 2009-2014. Mortality data up to December 31, 2019 were obtained using the National Death Index. The following CBC-derived inflammatory biomarkers were examined: neutrophil/lymphocyte ratio (NLR), neutrophil/(white blood cells - neutrophils) ratio (dNLR), monocyte count/lymphocyte ratio (MLR), (neutrophil + monocyte)/lymphocyte ratio (NMLR), platelet/lymphocyte ratio (PLR), and systemic inflammatory response index (SIRI). Weighted logistic and Cox regression analyses were used to calculate odds ratios, hazard ratios, and the corresponding 95% confidence intervals. Additionally, the prognostic value of the inflammatory indicators was assessed and ranked using the random survival forest approach. Results: In total, data from 21,431 participants with average age of 45.02 ± 0.27 years (49.51% male) were included in the study, among which 600 participants were positive for psoriasis (prevalence rate, 2.80%). Additionally, 79 all-cause deaths were recorded during a median follow-up period of 8.83 (6.67-11.00) years. Moreover, NLR, dNLR, NMLR, PLR, and SIRI were positively associated with the prevalence of psoriasis. Furthermore, MLR, NMLR, and SIRI were positively correlated with all-cause mortality in patients with psoriasis, with NMLR being the most valuable predictor of all-cause mortality. Conclusion: CBC-derived inflammatory biomarkers were associated with psoriasis prevalence, NMLR, SIRI, and MLR values were associated with all-cause mortality in patients with psoriasis. Overall, assessment of these CBC-derived indicators may serve as a simple method for screening high-risk individuals among patients with psoriasis.

5.
Cancer Gene Ther ; 30(12): 1649-1662, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37884580

RESUMO

Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The carcinogenic roles of lncRNA CALML3 antisense RNA 1 (CALML3-AS1) have been documented. However, the function and potential mechanisms of CALML3-AS1 in the progression of NSCLC need to be further explored. The molecule expression was assessed by qRT-PCR and Western blot. The subcellular localization of CALML3-AS1 was observed by fluorescence in situ hybridization (FISH). The malignant behaviors of NSCLC cells were evaluated by CCK-8, colony formation, EdU, wound healing and transwell assays. In vivo xenograft tumor and liver metastatic models were established. The molecular mechanisms were investigated by RIP, RNA pull-down and ChIP assays. The methylation level was detected by MSP. Herein, we found that CALML3-AS1 was upregulated, while butyrophilin-like 9 (BTNL9) was downregulated in NSCLC. Functionally, CALML3-AS1 depletion repressed NSCLC cell malignant phenotypes, in vivo tumor growth, and liver metastasis. Mechanistically, AlkB homolog 5 (ALKBH5) enhanced CALML3-AS1 stability via N6-methyladenosine (m6A) demethylation, whereas m6A reader YTH domain-containing 2 (YTHDC2) destabilized CALML3-AS1. Moreover, CALML3-AS1 inhibited BTNL9 transcription and expression through the recruitment of Zeste homolog 2 (EZH2). Rescue experiments demonstrated that BTNL9 downregulation counteracted sh-CALML3-AS1-mediated antitumor effects on NSCLC. Taken together, CALML3-AS1 modulated by ALKBH5 and YTHDC2 in an m6A modification dependent manner drives NSCLC progression via epigenetically repressing BTNL9.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Butirofilinas/genética , Butirofilinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metilação , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , /genética
6.
Mol Ecol ; 32(18): 4999-5012, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37525516

RESUMO

Genomic structural variations (SVs) are widespread in plant and animal genomes and play important roles in phenotypic novelty and species adaptation. Frequent whole genome duplications followed by (re)diploidizations have resulted in high diversity of genome architecture among extant species. In this study, we identified abundant genomic SVs in the Panax genus that are hypothesized to have occurred through during the repeated polyploidizations/(re)diploidizations. Our genome-wide comparisons demonstrated that although these polyploidization-derived SVs have evolved at distinct evolutionary stages, a large number of SV-intersecting genes showed enrichment in functionally important pathways related to secondary metabolites, photosynthesis and basic cellular activities. In line with these observations, our metabolic analyses of these Panax species revealed high diversity of primary and secondary metabolites both at the tissue and interspecific levels. In particular, genomic SVs identified at ginsenoside biosynthesis genes, including copy number variation and large fragment deletion, appear to have played important roles in the evolution and diversification of ginsenosides. A further herbivore deterrence experiment demonstrated that, as major triterpenoidal saponins found exclusively in Panax, ginsenosides provide protection against insect herbivores. Our study provides new insights on how polyploidization-derived SVs have contributed to phenotypic novelty and plant adaptation.


Assuntos
Ginsenosídeos , Panax , Saponinas , Ginsenosídeos/análise , Ginsenosídeos/química , Ginsenosídeos/metabolismo , Panax/genética , Panax/química , Panax/metabolismo , Variações do Número de Cópias de DNA , Saponinas/química , Saponinas/genética , Saponinas/metabolismo , Adaptação Fisiológica
7.
Plant J ; 115(6): 1500-1513, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37313760

RESUMO

Understanding how different driving forces have promoted biological divergence and speciation is one of the central issues in evolutionary biology. The Triticum/Aegilops species complex contains 13 diploid species belonging to the A-, B- and D-lineages and offers an ideal system to address the evolutionary dynamics of lineage fusion and splitting. Here, we sequenced the whole genomes of one S-genome species (Aegilops speltoides) of the B-lineage and four S*-genome diploid species (Aegilops bicornis, Aegilops longissima, Aegilops sharonensis and Aegilops searsii) of the D-lineage at the population level. We performed detailed comparisons of the five species and with the other four representative A-, B- and D-lineage species. Our estimates identified frequent genetic introgressions from A- and B-lineages to the D-lineage species. A remarkable observation is the contrasting distributions of putative introgressed loci by the A- and B-lineages along all the seven chromosomes to the extant D-lineage species. These genetic introgressions resulted in high levels of genetic divergence at centromeric regions between Ae. speltoides (B-lineage) and the other four S*-genome diploid species (D-lineage), while natural selection is a potential contributor to divergence among the four S*-genome species at telomeric regions. Our study provides a genome-wide view on how genetic introgression and natural selection acted together yet chromosome-regionally divided to promote genomic divergence among the five S- and S*-genome diploid species, which provides new and nuanced insights into the evolutionary history of the Triticum/Aegilops species complex.


Assuntos
Aegilops , Aegilops/genética , Filogenia , Triticum/genética , Diploide , Genoma de Planta/genética , Genômica , Seleção Genética
8.
Indian J Dermatol ; 68(1): 8-14, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151231

RESUMO

Objectives: Peripheral blood immune cell profiling of atopic dermatitis patients before and after treatment by single-cell RNA sequencing technique has not been reported. To study the immune Cell Profiling of Atopic Dermatitis Patients Before and After Treatment with Halometasone Cream Wet-Wrap Therapy. Methods: We used single cell sequencing to detect the proportion change and gene expression change of immune cells in 2 patients before and after treatment, and then used real-time PCR to confirm the mRNA level of differential genes. Results: In this study, scRNA-seq in two patients with severe AD before and after halometasone cream wet-wrap therapy showed that in the mild severity of AD after treatment, Th2 cells were significantly decreased (41.2% vs 13.4%), Th1 and Th17 cells were increased (23.3% vs 43.7%, 2.3% vs 4.8% respectively). The proportion of Th22 cells did not change much (1.3% vs 1.9%). Tregs were significantly increased also (1.5% vs 5.0%). In the regulatory T cells, the expression of IL-27, PD-1, CD103, CTLA-4, ZNF-66, IL-ß, CD7 gene was specifically increased after treatment, and CD39, P21, TOX2, CD151, CD79A, S100A12, TRAP1 gene was specifically decreased after treatment. In the TH2 cells, the expression of CD27, CD68, EZH1, RAD1, EGFR, CCR10, BCL11A, KLF4 gene was specifically increased after treatment and CCL26, CD180, IL-31, CCL22, LEF1, OX40 gene was specifically decreased after treatment. Conclusions: These genes may be new target for further study.

9.
Huan Jing Ke Xue ; 44(5): 2899-2907, 2023 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-37177961

RESUMO

The As sequestration by iron plaque and the As translocation in rice significantly affect the As accumulation in brown rice, and silicon (Si) application inhibits the As accumulation in rice plants. However, little information is available concerning the effect of Si application on As sequestration by iron plaque and translocation in rice. In this study, a pot experiment using As-contaminated paddy soil with different Si supply levels was conducted to investigate the effects of Si application on the As sequestration by iron plaque on the root surface and the As translocation from different tissues to brown rice. The results showed that the Si2 (0.66 g·kg-1) treatment significantly increased the activities of CAT (1.81 times), SOD (7.98 times), and POD (1.25 times) in the roots, increased the DCB-extractable Fe concentration (44.35%), and promoted the roughness of iron plaque (108.91%), resulting in a significant increase in the DCB-extractable As concentration of iron plaque (88.32%). Moreover, the Si2 treatment significantly promoted the As accumulation in the roots and inhibited the As translocation from the roots and leaves to the brown rice, leading to a significant decrease in the brown rice As concentration (53.12%). The increase in As sequestration by iron plaque with Si application was attributed to the enhancement of iron plaque formation and the promotion of surface roughness of iron plaque, whereas the inhibition of As translocation from the roots and leaves to the brown rice in the Si application treatment was closely related to the competition between Si with As for transporters and the promotion of As-thiol complex formation and As compartmentalization in vacuolar. These findings provide more insight into the mechanisms of As translocation in rice and will be helpful for exploring strategies to reduce rice grain As through Si supply in As-contaminated paddy fields in South China.


Assuntos
Arsênio , Oryza , Poluentes do Solo , Ferro/análise , Arsênio/análise , Silício/farmacologia , Silício/análise , Solo , Raízes de Plantas/química , Poluentes do Solo/análise , Cádmio/análise
10.
Ann Bot ; 130(5): 749-762, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-35961674

RESUMO

BACKGROUND AND AIMS: Elucidating how plant species respond to variable light conditions is important to understand the ecological adaptation to heterogeneous natural habitats. Plant performance and its underlying gene regulatory network have been well documented in sun-grown plants. However, the phenotypic and molecular responses of shade-grown plants under variable light conditions have remained largely unclear. METHODS: We assessed the differences in phenotypic performance between Panax ginseng (shade-grown) and Arabidopsis thaliana (sun-grown) under sunlight, shade and deep-shade conditions. To further address the molecular bases underpinning the phenotypic responses, we compared time-course transcriptomic expression profiling and candidate gene structures between the two species. KEY RESULTS: Our results show that, compared with arabidopsis, ginseng plants not only possess a lower degree of phenotypic plasticity among the three light conditions, but also exhibit higher photosynthetic efficiency under shade and deep-shade conditions. Further comparisons of the gene expression and structure reveal that differential transcriptional regulation together with increased copy number of photosynthesis-related genes (e.g. electron transfer and carbon fixation) may improve the photosynthetic efficiency of ginseng plants under the two shade conditions. In contrast, the inactivation of phytochrome-interacting factors (i.e. absent and no upregulation of the PIF genes) are potentially associated with the observed low degree of phenotypic plasticity of ginseng plants under variable light conditions. CONCLUSIONS: Our study provides new insights into how shade-grown plants respond to variable light conditions. Candidate genes related to shade adaptation in ginseng provide valuable genetic resources for future molecular breeding of high-density planting crops.


Assuntos
Arabidopsis , Panax , Panax/genética , Panax/metabolismo , Transcriptoma , Luz , Arabidopsis/genética , Fotossíntese/genética
11.
Cell Death Dis ; 13(7): 657, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902569

RESUMO

Gefitinib has been widely applied for the treatment of lung adenocarcinoma (LUAD). However, the long-term application of gefitinib usually leads to acquired drug resistance in tumour patients, resulting in clinical treatment failure. Small nucleolar host gene 17 (SNHG17) has been shown to play a regulatory role in LUAD progression. Nevertheless, the role of SNHG17 in LUAD gefitinib resistance remains elusive. The expression pattern of SNHG17 was examined in tissues and cell lines of gefitinib-sensitive and gefitinib-resistant LUAD, respectively. Gain- and loss-of-function experiments were employed to assess the biological functions of SNHG17 in cell proliferation and apoptosis, as well as aggressive phenotypes of LUAD cells. MeRIP-qPCR and colorimetric quantificational analysis were performed to detect m6A modifications and contents. Fluorescence in situ hybridisation (FISH) and subcellular fractionation analysis were used to reveal the distribution of SNHG17. RIP and ChIP assays were performed to further validate the SNHG17/EZH2/LATS2 regulatory axis. A xenograft tumour growth assay was conducted to evaluate the role of SNHG17 in LUAD gefitinib resistance in vivo. SNHG17 was upregulated in gefitinib-resistant LUAD tissues and cell lines. Functional assays showed that SNHG17 aggravated the malignant phenotypes of gefitinib-resistant LUAD cells. In addition, METTL3-mediated N6-methyladenosine modification could induce the upregulation of SNHG17by stabilising its RNA transcript. Mechanistically, SNHG17 epigenetically repressed the expression of LATS2 by recruiting EZH2 to the promoter region of LATS2. The regulatory role of the SNHG17/EZH2/LATS2 axis in LUAD gefitinib resistance was further supported in vivo. Collectively, our findings suggested that SNHG17 induced by METTL3 could promote LUAD gefitinib resistance by epigenetically repressing LATS2 expression.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , RNA Longo não Codificante , Adenocarcinoma/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Gefitinibe/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metiltransferases/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
12.
Front Med (Lausanne) ; 9: 899857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755046

RESUMO

Background: The clinical features of urticaria have not been fully illustrated. Objectives: To demonstrate clinical features of urticaria in different areas of southern and northern China. Methods: In this hospital-based multicenter study, outpatients with urticaria filled in a questionnaire during the initial visit and follow-up (once per week, lasting for a month). Results: Overall, 1,715 outpatients with urticaria with a mean age of 37.86 ± 16.08 years (range = 0.5-87 years) were recruited. The median disease duration was 1.94 ± 4.31 years (range = 0-58 years). More itching was observed in the northern areas higher than that in the southern areas (99.5 vs 94.1%, P < 0.001). The incidence of pain, arthralgia, and family history in southern areas was higher than that in northern areas (5.1 vs 1.1%, 9.6 vs 0, 10.6% vs 3.2%, P < 0.001). The leading subtypes of specified urticaria were chronic spontaneous urticaria (81.4%) and symptomatic dermographism (35.9%). The incidence of symptomatic dermographism and cold urticaria in the southern areas was lower than that in the northern areas (31.8 vs. 50.3%, 4 vs. 8.5%, P < 0.001). Allergic diseases were the most common concomitant disorders of urticaria. More than half of the patients had to avoid certain food, such as fish-prawn-crab (30.7%) and alcohol (20%). Ebastine (41.1%) was the most commonly prescribed drug. The disease duration negatively correlated with the severity of itching and number of wheals (>50/24H) (Spearman's rank correlation test, p < 0.001). Conclusion: This study provides a profile of clinical characteristics of urticaria in China and filled the gap in the field of regional comparative studies on urticaria.

13.
New Phytol ; 235(5): 2066-2080, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35637631

RESUMO

Sympatric genetic divergence is the most appealing and controversial pattern in the theory of ecological speciation. Examples that support sympatric genetic divergence in plant species are extremely rare. Solid evidence of sympatric genetic divergence will provide deep insights for revealing the underlying mechanisms of ecological speciation. We analysed the total genomic DNA sequences of 120 weedy rice (WR; Oryza sativa f. spontanea) plants, representing three WR population pairs separately from three early- and late-season rice fields, in comparison with those of the co-occurring rice cultivars and other rice materials. We detected substantial genetic divergence within the pairs of the sympatric early- and late-season WR populations, although genetic divergence was unevenly distributed across the genomes. Restricted gene flow was determined between the sympatric WR populations, resulting in their distinct genetic structures. We also detected relatively low genetic diversity that was likely to be associated with stronger selection in early-season WR populations. Our findings provide strong evidence for sympatric genetic divergence between the WR populations in the same fields but in different seasons. We conclude that temporal isolation plays an important role in creating genetic divergence between sympatric populations/species in plants.


Assuntos
Oryza , Fluxo Gênico , Especiação Genética , Variação Genética , Oryza/genética , Plantas Daninhas , Estações do Ano , Simpatria
14.
Nat Commun ; 13(1): 1902, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35393424

RESUMO

All extant core-eudicot plants share a common ancestral genome that has experienced cyclic polyploidizations and (re)diploidizations. Reshuffling of the ancestral core-eudicot genome generates abundant genomic diversity, but the role of this diversity in shaping the hierarchical genome architecture, such as chromatin topology and gene expression, remains poorly understood. Here, we assemble chromosome-level genomes of one diploid and three tetraploid Panax species and conduct in-depth comparative genomic and epigenomic analyses. We show that chromosomal interactions within each duplicated ancestral chromosome largely maintain in extant Panax species, albeit experiencing ca. 100-150 million years of evolution from a shared ancestor. Biased genetic fractionation and epigenetic regulation divergence during polyploidization/(re)diploidization processes generate remarkable biochemical diversity of secondary metabolites in the Panax genus. Our study provides a paleo-polyploidization perspective of how reshuffling of the ancestral core-eudicot genome leads to a highly dynamic genome and to the metabolic diversification of extant eudicot plants.


Assuntos
Genoma de Planta , Panax , Cromatina/genética , Cromossomos , Epigênese Genética , Evolução Molecular , Genoma de Planta/genética , Panax/genética , Filogenia , Poliploidia
15.
Biomed Res Int ; 2022: 4084121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35155673

RESUMO

BACKGROUND: Atopic dermatitis (AD) has long been hypothesized to be associated with risk of depression and suicide, but the causal relationship between them is still unclear. OBJECTIVE: To evaluate the causality between AD, depression, and suicide using a Mendelian randomization (MR) approach. METHOD: We extracted summary-level data for AD, major depression, and suicidal ideation or attempt from published, nonoverlapping genome-wide association studies (GWAS). Inverse variance-weighted (IVW) analysis was used as the primary analysis. Alternate methods, including weighted median, MR Egger, MR pleiotropy residual sum and outlier, weighted mode, and leave-out analysis, were performed to assess pleiotropy. RESULTS: 13 SNPs (13,287 cases and 41,345 controls) were selected as instrumental variables (IVs). The IVW analysis indicated a statistically significant but small causal effect of AD on major depression (OR = 1.027, 95% CI 1.004-1.050; p = 0.020). No significant evidence was observed for a causal effect of AD on suicide. No significant effect of pleiotropy was found. CONCLUSION: AD has a significant but small effect on major depression, but not on suicide.


Assuntos
Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Dermatite Atópica/genética , Dermatite Atópica/psicologia , Análise da Randomização Mendeliana , Ideação Suicida , Causalidade , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único
16.
Am J Cancer Res ; 12(1): 265-279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35141017

RESUMO

There are numerous antibodies used for cancer therapy in clinic, but they are essentially less efficacy than expected. None of them has tumor-specific and broad-spectral properties. PIWIL2-like (PL2L) protein 60 (PL2L60) is a product of alienated activation of PIWIL2 gene, and has been found to be specifically and widely expressed in various types of cancers, including hematopoietic and solid ones. Current study aims to investigate whether a monoclonal antibody (mAb) to PL2L60 has both tumor-specific and broad-spectral properties, which can be used universally to treat various types of cancers. The expression of PL2L60 protein in the cell surface and cytoplasm were determined in a panel of human and mouse tumor cell lines by flow cytometry, immunofluorescent microscopy and Western Blotting. The apoptosis and the cell cycle arrest of the tumor cells treated with mAb KAO3 were evaluated by flow cytometry. The tumorigenesis of the mAb KAO3-pretreated tumor cells was determined by tumor incidence and tumor size, and the efficacy of mAb KAO3 treatment on tumor growth in tumors-bearing mice were kinetically evaluated. Complement-dependent cytotoxicity (CDC) assay was used to determine the capacity of mAb KAO3 to kill tumor cells. Treatment of human or mouse tumor cells from hematopoietic or solid tumors with mAb KAO3 at the time of inoculation efficiently inhibited tumorigenesis in the severe combined immunodeficient (SCID) mice. Moreover, injection of mAb KAO3 into established tumors significantly inhibited their growth, and prolonged survival of the tumor-bearing mice, including lymphoma, breast cancer, lung cancer and cervical cancer. The efficacy of mAb KAO3 treatment is likely associated with its binding to PL2L60 expressed on tumor cell surface, which may lead to cancer cell death through blocking cell cycling and/or activation of complement. In conclusion, we have identified a tumor-specific mAb to PL2L60 (KAO3), which may be used potentially to treat all the types of human cancers including from both hematopoietic and solid ones.

17.
Huan Jing Ke Xue ; 43(1): 472-480, 2022 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-34989532

RESUMO

The bioavailability of heavy metals in soil and the physiological activities of rice determine the accumulation of heavy metals in brown rice. In this study, a field experiment was conducted in a rice paddy in which the total amount of Cd in the soil did not exceed the national standard, whereas the Cd in rice grains was at risk of overreaching in the suburbs of Guangzhou city. The bioavailability of heavy metals in the soil and the physiological barrier of rice were taken as the starting point. The early and late rice yield, brown rice heavy metal content, Cd and Pb enrichment coefficient, total soil heavy metals, soil physical and chemical properties, and soil Cd and Pb species distribution were investigated under the Si-rich amendment (JD), Ca-Mg amendment (YY), Si-rich amendment+flooding irrigation (JD+YS), and Ca-Mg amendment+flooding irrigation (YY+YS) treatments. The results showed that:① the total ω(Cd) in the soil was only 0.13 mg·kg-1 in the CK treatment. However, the average ω(Cd) in the grain of early rice reached up to 0.19 mg·kg-1. The early rice varieties (hybrid rice) had a more vital ability to accumulate Cd and total As in brown rice than that in late rice varieties (conventional rice) but a lower capacity for Pb accumulation. ② JD and YY application alone had no noticeable inhibitory effect on the accumulation of Cd and Pb in brown rice; however, JD+YS and YY+YS treatments significantly inhibited the accumulation of Cd and Pb in brown rice in both early and late rice, especially in the JD+YS treatment, which decreased the Cd and Pb accumulation by 65.8% and 68% for early rice and by 71.43% and 49.15% for late rice, respectively. The primary mechanism of JD+YS was to increase soil pH and maintain a low redox potential to promote soil Cd and Pb to be transformed from acid-soluble to a reduced state and residue state, thus decreasing Cd and Pb to migrate from the soil to the rice. At the same time, it effectively suppressed the absorption and transportation of Cd and Pb by early and late rice via the physiological barrier effect of Si nutrition and the competition for transportation channels between calcium and magnesium ions and cadmium and inhibited the accumulation of Cd and Pb in the brown rice of early and late rice. These results provide a theoretical basis for the exploration and application of the control technologies in the brown rice Cd and Pb resistance and have important practical significance for guiding the safe production in the rice-growing area in South China.


Assuntos
Oryza , Poluentes do Solo , Cádmio/análise , Chumbo , Solo , Poluentes do Solo/análise , Água , Abastecimento de Água
18.
Mol Plant ; 15(3): 488-503, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-34979290

RESUMO

Common wheat (Triticum aestivum, BBAADD) is a major staple food crop worldwide. The diploid progenitors of the A and D subgenomes have been unequivocally identified; that of B, however, remains ambiguous and controversial but is suspected to be related to species of Aegilops, section Sitopsis. Here, we report the assembly of chromosome-level genome sequences of all five Sitopsis species, namely Aegilops bicornis, Ae. longissima, Ae. searsii, Ae. sharonensis, and Ae. speltoides, as well as the partial assembly of the Amblyopyrum muticum (synonym Aegilops mutica) genome for phylogenetic analysis. Our results reveal that the donor of the common wheat B subgenome is a distinct, and most probably extinct, diploid species that diverged from an ancestral progenitor of the B lineage to which the still extant Ae. speltoides and Am. muticum belong. In addition, we identified interspecific genetic introgressions throughout the evolution of the Triticum/Aegilops species complex. The five Sitopsis species have various assembled genome sizes (4.11-5.89 Gb) with high proportions of repetitive sequences (85.99%-89.81%); nonetheless, they retain high collinearity with other genomes or subgenomes of species in the Triticum/Aegilops complex. Differences in genome size were primarily due to independent post-speciation amplification of transposons. We also identified a set of Sitopsis genes pertinent to important agronomic traits that can be harnessed for wheat breeding. These newly assembled genome resources provide a new roadmap for evolutionary and genetic studies of the Triticum/Aegilops complex, as well as for wheat improvement.


Assuntos
Aegilops , Aegilops/genética , Genoma de Planta/genética , Filogenia , Melhoramento Vegetal , Poliploidia , Triticum/genética
19.
J Cosmet Dermatol ; 21(5): 2200-2204, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34333850

RESUMO

BACKGROUND: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) refers to an uncommon cutaneous adverse reaction that symmetrically involves the buttock and intertriginous areas after systemic exposure to the offending drug and is previously known as baboon syndrome. SDRIFE related with traditional Chinese medicine (TCM) has not been reported. OBJECTIVE: We presented a case of SDRIFE /baboon syndrome induced by TCM, Xi-Huang capsule. METHODS: A 57-years-old man presented with macular erythematous rash mainly on his intergluteal, inguinal, axillary, popliteal regions for a duration of 5 days. The lesions appeared a day after an oral Chinese patent medicine Xi-Huang capsule for arthralgia. Drug eruption was diagnosed. The rash disappeared completely within a week with immediate discontinuation of Xi-Huang capsule and a short term of systemic therapy with glucocorticosteroids. Patch testing was performed on the patient 1 month after complete resolution. He was patch tested with Xi-Huang capsule (5% and 10% in petroleum) using Finn Chambers on Scanpor tape and T.R.U.E. test system. Five heathy volunteers were also patch tested with the same Xi-Huang capsule. RESULTS: Patch testing to 20 common contact allergens including nickel and fragrance were negative. TCM patch test was positive. No positive results were found in five volunteers. Months later, the patient relapsed after an oral herbal Chinese medicine challenge for arthralgia. To avoid the rash recurrence, he stopped taking any Chinese herbal medicine and had complete resolution of disease. CONCLUSION: The Chinese patent drugs for external and oral have unique advantages and have been widely used in many diseases. It is important that dermatologists monitor for clinically significant manifestations of TCM, such as baboon syndrome. Patch testing could help make a definitive diagnosis.


Assuntos
Erupção por Droga , Exantema , Intertrigo , Animais , Artralgia , Erupção por Droga/diagnóstico , Erupção por Droga/tratamento farmacológico , Erupção por Droga/etiologia , Exantema/induzido quimicamente , Exantema/diagnóstico , Exantema/patologia , Humanos , Intertrigo/induzido quimicamente , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Papio
20.
Biomed Res Int ; 2021: 5528372, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195265

RESUMO

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.


Assuntos
Produtos Biológicos/uso terapêutico , Dermatite Atópica/terapia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Doença Crônica , Humanos , Sistema Imunitário , Inflamação , Interleucina-33/antagonistas & inibidores , Interleucinas/antagonistas & inibidores , Segurança do Paciente , Receptores OX40/antagonistas & inibidores , Resultado do Tratamento
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