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Purpose: Cigarette smoking is the most recognized risk factor of chronic obstructive pulmonary disease (COPD) in China. However, there are no studies analyzing the impact of different smoking behaviors on pulmonary function and pulmonary hypertension (PH) among Chinese male patients with COPD. Patients and Methods: Chinese male smokers with COPD performed pulmonary function tests. Clinical characteristics, smoking behavior features, spirometry and echocardiographic results were compared between the two groups stratified by initial smoking age (18 years old) or complicated PH. Results: The early-smoking group had more respiratory symptoms, more severe smoking behavior, worse pulmonary function with lower FEV1%pre (38.5% vs 70.2%) and FEV1/FVC% (47.5% vs 63.8%), and higher systolic pulmonary artery pressure (sPAP: 38.6 vs 33.9 mmHg) than the late-smoking group. Initiating smoking before adulthood was an independently contributing factor of ventilatory dysfunction and Global Initiative for Obstructive Lung Disease (GOLD) stage escalation. It also had a significant interaction with long smoking duration (≥30 years), characterized by markedly decreased lung volumes (VC%pre: 64.0% vs 84.5%), impaired diffusing capacity (DLCO%pre: 58.0% vs 76.8%) and severe emphysema (RV/TLC%pre: 145.2% vs 130.2%). COPD patients complicated with PH exhibited worse ventilatory function (FEV1%pre: 43.2% vs 56.2%), impaired diffusion capacity (DLCO%pre: 56.7% vs 77.1%) and decreased lung volume (VC%pre: 67.67% vs 75.38%). Both severe smoking behaviors and impaired pulmonary function had close correlations with sPAP. Conclusion: The early-smoking group exhibited predominantly ventilation dysfunction and had complex interactions with long smoking duration to further affect lung volume and diffusion capacity. Different smoking behaviors influenced variations of pulmonary dysfunction and comorbid PH in patients with COPD.
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Hipertensión Pulmonar , Pulmón , Enfermedad Pulmonar Obstructiva Crónica , Fumar , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Persona de Mediana Edad , Pulmón/fisiopatología , China/epidemiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Factores de Riesgo , Anciano , Volumen Espiratorio Forzado , Fumar/efectos adversos , Fumar/epidemiología , Capacidad Vital , Espirometría , Capacidad de Difusión Pulmonar , Factores de Tiempo , Índice de Severidad de la Enfermedad , Fumadores , Presión Arterial , Arteria Pulmonar/fisiopatología , Estudios Transversales , Pueblos del Este de AsiaRESUMEN
Ovarian cancer has the highest mortality among gynecological malignancies, and exploring effective strategies to reverse the immunosuppressive tumor microenvironment in patients remains a pressing scientific challenge. In this study, we identified a pyroptosis-related protective factor, GBP5, which significantly inhibits the growth of ovarian cancer cells and patient-derived ovarian cancer organoids, impeding the invasion and migration of ovarian cancer cells. Results of immunohistochemistry and external single-cell data verification were consistent. Further research confirmed that GBP5 in ovarian cancer cell can induce canonical pyroptosis through JAK2/STAT1 pathway, thereby restraining the progression of ovarian cancer. Interestingly, in this study, we also discovered that ovarian cancer cells with high GBP5 expression exhibit increased expressions of CXCL9/10/11 in a co-culture assay. Subsequent immune cell infiltration analyses revealed the remodeling of immunosuppressive microenvironment in ovarian cancer patients, characterized by increased infiltration and polarization of M1 macrophages. External immunotherapy database analysis showed profound potential for the application of GBP5 in immunotherapy strategies for ovarian cancer. Overall, our study demonstrates that the protective factor GBP5 significantly inhibits ovarian cancer progression, triggering canonical pyroptosis through the JAK2-STAT1 pathway. Driven by its pro-inflammatory nature, it can also enhance M1 macrophages polarization and reverse immunosuppressive microenvironment, thus providing new insights for ovarian cancer treatment.
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Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO2 nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO2-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a H2O2-driven black TiO2 mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO2 nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO2 nanosphere. The overexpressed H2O2 can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO2 and PMO compartments in the Janus nanostructure, TiO2&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous H2O2 within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO2, leading to intensified PDT effects and effective tumor inhibition.
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Rayos Infrarrojos , Fotoquimioterapia , Fármacos Fotosensibilizantes , Titanio , Titanio/química , Titanio/farmacología , Humanos , Porosidad , Animales , Ratones , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Nanoestructuras/química , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Tamaño de la PartículaRESUMEN
The research of plant seeds has always been a focus of agricultural and forestry research, and seed identification is an indispensable part of it. With the continuous application of artificial intelligence technology in the field of agriculture, seed identification through computer vision can effectively promote the development of agricultural and forestry wisdom. Data is the foundation of computer vision, but there is a lack of suitable datasets in the agricultural field. In this paper, a seed dataset named LZUPSD is established. A device based on mobile phones and macro lenses was established to acquire images. The dataset contains 4496 images of 88 different seeds. This dataset can not only be used as data for training deep learning models in the computer field, but also provide important data support for agricultural and forestry research. As an important resource in this field, this dataset plays a positive role in modernizing agriculture and forestry.
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Inteligencia Artificial , Semillas , Agricultura , Agricultura ForestalRESUMEN
BACKGROUND: Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) has demonstrated unprecedented potential in the treatment of POF. However, the heterogeneity of human UC-MSCs remains a challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within UC-MSCs that possess the capability to improve ovarian function, with the aim of reducing the uncertainty arising from the heterogeneity while achieving more effective treatment of POF. METHODS: 10 × Genomics was performed to investigate the heterogeneity of human UC-MSCs. We used LRP1 as a marker and distinguished the potential therapeutic subpopulation by flow cytometry, and determined its secretory functions. Unsorted UC-MSCs, LRP1high and LRP1low subpopulation was transplanted under the ovarian capsules of aged mice and CTX-induced POF mice, and therapeutic effects was evaluated by assessing hormone levels, estrous cycles, follicle counts, and embryo numbers. RNA sequencing on mouse oocytes and granulosa cells after transplantation was performed to explore the mechanism of LRP1high subpopulation on mouse oocytes and granulosa cells. RESULTS: We identified three distinct functional subtypes, including mesenchymal stem cells, multilymphoid progenitor cells and trophoblasts. Additionally, we identified the LRP1high subpopulation, which improved ovarian function in aged and POF mice. We elucidated the unique secretory functions of the LRP1high subpopulation, capable of secreting various chemokines, cytokines, and growth factors. Furthermore, LRP1 plays a crucial role in regulating the ovarian microenvironment, including tissue repair and extracellular matrix remodeling. Consistent with its functions, the transcriptomes of oocytes and granulosa cells after transplantation revealed that the LRP1high subpopulation improves ovarian function by modulating the extracellular matrix of oocytes, NAD metabolism, and mitochondrial function in granulosa cells. CONCLUSION: Through exploration of the heterogeneity of UC-MSCs, we identified the LRP1high subpopulation capable of improving ovarian function in aged and POF mice by secreting various factors and remodeling the extracellular matrix. This study provides new insights into the targeted exploration of human UC-MSCs in the precise treatment of POF.
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Células Madre Mesenquimatosas , Insuficiencia Ovárica Primaria , Humanos , Femenino , Animales , Ratones , Anciano , Insuficiencia Ovárica Primaria/terapia , Oocitos , Células Madre , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genéticaRESUMEN
BACKGROUND: Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position. METHODS: Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient. RESULTS: Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions. CONCLUSIONS: Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.
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Síndrome de Dificultad Respiratoria , Tomografía Computarizada por Rayos X , Masculino , Femenino , Porcinos , Animales , Impedancia Eléctrica , Síndrome de Dificultad Respiratoria/terapia , Pulmón , Perfusión , Tomografía/métodosRESUMEN
BACKGROUND: This study aimed to investigate the underlying molecular mechanisms of TRIM58 in the development of colorectal cancer (CRC). CRC is one of the most common cancers of the digestive tract worldwide. The ubiquitin-proteasome system regulates many oncogenic or tumor-suppressive proteins. TRIM58, an E3 ubiquitin ligase and a member of the tripartite motif protein family, is a potential prognostic marker that indicates poor prognosis in cancer. Currently, the precise molecular mechanisms for the TRIM58-mediated CRC progression remain unclear. METHODS: To examine the effects of TRIM58 on cell viability, cell cycle progression, and apoptosis in CRC, Cell Counting Kit-8 and flow cytometry assays were employed. The AKT inhibitor LY294002 was used to examine the effects of AKT signaling on TRIM58-mediated cell viability, cell cycle progression, and apoptosis in CRC. Additionally, Co-IP and ubiquitination assays were used to examine the correlation between TRIM58 and RECQL4. RESULTS: TRIM58 overexpression inhibited CRC cell viability and promoted cell cycle arrest and apoptosis, in which the TRIM58 knockdown demonstrated inversed effects via the AKT signaling pathway. TRIM58 inhibited RECQL4 protein levels through its ubiquitin ligase activity, and RECQL4 overexpression inhibited TRIM58 overexpression-mediated CRC cell viability, cell cycle progression, and apoptosis. The downregulation of TRIM58 and upregulation of RECOL4 were observed in human CRC tissue, and TRIM58 demonstrated antitumor effects in CRC-induced tumor growth in a mouse model. CONCLUSIONS: TRIM58 acts as a tumor suppressor in CRC through the promotion of RECQL4 ubiquitination and inhibition of the AKT signaling pathway and may be investigated for the successful treatment of CRC.
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Neoplasias Colorrectales , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Ratones , RecQ Helicasas , Transducción de Señal , Ubiquitinación , UbiquitinasRESUMEN
OBJECTIVE: This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). METHODS: Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway. RESULTS: Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon. CONCLUSION: Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.
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Colitis , Enfermedad de Crohn , Moxibustión , Ratas , Animales , Enfermedad de Crohn/terapia , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Moxibustión/métodos , Receptor Toll-Like 4/metabolismo , Ratas Sprague-Dawley , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Inflamación , Circulación Enterohepática , ARN Mensajero/metabolismoRESUMEN
Cervical cancer (CC) is a malignancy that tends to have a poor prognosis when detected at an advanced stage; however, there are few studies on the early detection of CC at the genetic level. The tumor microenvironment (TME) and genomic instability (GI) greatly affect the survival of tumor patients via effects on carcinogenesis, tumor growth, and resistance. It is necessary to identify biomarkers simultaneously correlated with components of the TME and with GI, as these could predict the survival of patients and the efficacy of immunotherapy. In this study, we extracted somatic mutational data and transcriptome information of CC cases from The Cancer Genome Atlas, and the GSE44001 dataset from the Gene Expression Omnibus database was downloaded for external verification. Stromal components differed most between genomic unstable and genomic stable groups. Differentially expressed genes were screened out on the basis of GI and StromalScore, using somatic mutation information and ESTIMATE methods. We obtained the intersection of GI- and StromalScore-related genes and used them to establish a four-gene signature comprising RIPOR2, CCL22, PAMR1, and FBN1 for prognostic prediction. We described immunogenomic characteristics using this risk model, with methods including CIBERSORT, gene set enrichment analysis (GSEA), and single-sample GSEA. We further explored the protective factor RIPOR2, which has a close relationship with ImmuneScore. A series of in vitro experiments, including immunohistochemistry, immunofluorescence, quantitative reverse transcription PCR, transwell assay, CCK8 assay, EdU assay, cell cycle detection, colony formation assay, and Western blotting were performed to validate RIPOR2 as an anti-tumor signature. Combined with integrative bioinformatic analyses, these experiments showed a strong relationship between RIPOR2 with tumor mutation burden, expression of genes related to DNA damage response (especially PARP1), TME-related scores, activation of immune checkpoint activation, and efficacy of immunotherapy. To summarize, RIPOR2 was successfully identified through comprehensive analyses of the TME and GI as a potential biomarker for forecasting the prognosis and immunotherapy response, which could guide clinical strategies for the treatment of CC patients.
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Neoplasias del Cuello Uterino , Biomarcadores de Tumor/genética , Femenino , Inestabilidad Genómica , Humanos , Pronóstico , Microambiente Tumoral/genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
The METTL3-METTL14 complex, the "writer" of N6-methyladenosine (m6A), plays an important role in many biological processes. Previous studies have shown that Mettl3 overexpression can increase the level of m6A and promote somatic cell reprogramming. Here, we demonstrate that Mettl14, another component of the methyltransferase complex, can significantly enhance the generation of induced pluripotent stem cells (iPSCs) in an m6A-independent manner. In cooperation with Oct4, Sox2, Klf4, and c-Myc, overexpressed Mettl14 transiently promoted senescence-associated secretory phenotype (SASP) gene expression in non-reprogrammed cells in the late stage of reprogramming. Subsequently, we demonstrated that interleukin-6 (IL-6), a component of the SASP, significantly enhanced somatic cell reprogramming. In contrast, blocking the SASP using a senolytic agent or a nuclear factor κB (NF-κB) inhibitor impaired the effect of Mettl14 on reprogramming. Our results highlight the m6A-independent function of Mettl14 in reprogramming and provide new insight into the interplay between senescence and reprogramming in vitro.
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Reprogramación Celular , Células Madre Pluripotentes Inducidas , Reprogramación Celular/genética , Células Madre Pluripotentes Inducidas/metabolismo , Factor 4 Similar a Kruppel , Fenotipo Secretor Asociado a la SenescenciaRESUMEN
Fibrosis can occur in many organs, and severe cases leading to organ failure and death. No specific treatment for fibrosis so far. In recent years, microRNA-34a (miR-34a) has been found to play a role in fibrotic diseases. MiR-34a is involved in the apoptosis, autophagy and cellular senescence, also regulates TGF-ß1/Smad signal pathway, and negatively regulates the expression of multiple target genes to affect the deposition of extracellular matrix and regulate the process of fibrosis. Some studies have explored the efficacy of miR-34a-targeted therapies for fibrotic diseases. Therefore, miR-34a has specific potential for the treatment of fibrosis. This article reviews the important roles of miR-34a in fibrosis and provides the possibility for miR-34a as a novel therapeutic target in fibrosis.
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Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Bile acids (BAs) can be used as effector molecules to regulate physiological processes in the gut, and NRs are important receptors for bile acid signaling. Relevant studies have shown that NRs are closely related to the occurrence of Crohn's disease (CD). Although the mechanism of NRs in CD has not been clarified completely, growing evidence shows that NRs play an important role in regulating intestinal immunity, mucosal barrier, and intestinal flora. NRs can participate in the progress of CD by mediating inflammation, immunity, and autophagy. As the important parts of traditional Chinese medicine (TCM) therapy, acupuncture and moxibustion in the treatment of CD curative mechanism can get a lot of research support. At the same time, acupuncture and moxibustion can regulate the changes of related NRs. Therefore, to explore whether acupuncture can regulate BA circulation and NRs expression and then participate in the disease progression of CD, a new theoretical basis for acupuncture treatment of CD is provided.
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Background: Cervical cancer (CC) has long been a concern, as a gynecological cancer type of high-risk. At present, there are few studies on the early detection of CC at the genetic level. The breakthrough is to recognize CC patients tending to have a worse prognosis by checking the expression pattern of ferroptosis-related genes, which enjoy a great potential of being applied to cancer treatment. Methods: Data used in this study was obtained from a series of public online databases, integrated with ferroptosis-related gene collection stored from the FerrDb database and GeneCards database. The least absolute shrinkage and selection operator- (LASSO-) penalized analysis was taken for modeling, and before, univariate Cox regression analysis got done to shrink the candidates' range. Several analyses were made for the evaluation of the efficacy of the new model, based on CC patients' overall survival (OS). Tumor microenvironment- (TME-) related analyses were conducted by various algorithms on different populations, comprising CIBERSORT, ssGSEA, XCELL, etc. Nonnegative matrix factorization (NMF) clustering got applied to find that ferroptosis-marker genes affect prognosis more than "driver" and "suppressor". Hub-gene PTGS2 was screened out by protein-protein interaction analysis and real-time qPCR after ferroptosis induction, and ELISA was conducted for further verification on the correlation between ferroptosis and M1 polarization. Results: The twenty-five ferroptosis-related genes model can estimate the prognosis of patients independently of other clinical factors, and the low-risk score group shows higher expression of immune-enhancing cells, noteworthily for M1 macrophages. It is experimentally validated that the M1 marker TNF-α significantly increased after coculturing M1 macrophages and SiHa cells processed with ferroptosis inductor before. The key gene to the model, PTGS2, presented to be a risk factor in cervical cancer, and its low-expression group has stronger immune activity and higher tumor mutation burden, with the significantly highly mutated gene TENM2 in it showing high drug sensitivity and neoantigen for patients with its mutant-type. Meanwhile, it influences macrophage polarization. Conclusion: Prognosis of early-stage cervical cancer patients can be exactly predicted on ferroptosis-related genes. Among model genes, PTGS2 may have a major impact by affecting macrophage polarization and mutation effects.
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Drought is a major environmental constraint that causes substantial reductions in plant growth and yield. Expression of stress-related genes is largely regulated by transcription factors (TFs), including in soybean [Glycine max (L.) Merr.]. In this study, 301 GmAP2/ERF genes that encode TFs were identified in the soybean genome. The TFs were divided into five categories according to their homology. Results of previous studies were then used to select the target gene GmAP2/ERF144 from among those up-regulated by drought and salt stress in the transcriptome. According to respective tissue expression analysis and subcellular determination, the gene was highly expressed in leaves and encoded a nuclear-localized protein. To validate the function of GmAP2/ERF144, the gene was overexpressed in soybean using Agrobacterium-mediated transformation. Compared with wild-type soybean, drought resistance of overexpression lines increased significantly. Under drought treatment, leaf relative water content was significantly higher in overexpressed lines than in the wild-type genotype, whereas malondialdehyde content and electrical conductivity were significantly lower than those in the wild type. Thus, drought resistance of transgenic soybean increased with overexpression of GmAP2/ERF144. To understand overall function of the gene, network analysis was used to predict the genes that interacted with GmAP2/ERF144. Reverse-transcription quantitative PCR showed that expression of those interacting genes in two transgenic lines was 3 to 30 times higher than that in the wild type. Therefore, GmAP2/ERF144 likely interacted with those genes; however, that conclusion needs to be verified in further specific experiments.
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BACKGROUND: Gastric mucosal lesions (GML) are common in gastric diseases and seriously affect the quality of life. There are inevitable side effects in drug therapy. Acupuncture is an important part of traditional Chinese medicine. Electro-acupuncture (EA) has unique curative effect in treatment of GML. However, there are still few reports on the central mechanism of electro-acupuncture in treatment of GML. In this study, NMR metabonomics was used to explore the central metabolic change mechanism of electro-acupuncture in treatment of GML. METHODS: SD rats were randomly divided into Control, GML and EA groups. According to different intervention time, each group was further divided into 3 subgroups. This study mainly established GML model rats by 75% ethanol. Dynamic expressions of metabolites in cerebral cortex and medulla were observed by 1D 1H Nuclear Magnetic Resonance (NMR) metabolomics, combined with gastric mucosal histopathological examination to evaluate the time-effect relationship of electro-acupuncture at Zusanli (ST36) and Liangmen (ST21) points for 1 day, 4 days and 7 days treatment of GML. RESULTS: The results showed that the repair effect of electro-acupuncture on gastric mucosal injury was the most obvious in 4 days and stable in 7 days, and 4 days electro-acupuncture can effectively inhibit GML gastric mucosal inflammation and the expression of inflammatory cells. Meanwhile, the NMR spectrum results of medulla and cerebral cortex showed that, 21 potential metabolites were identified to participate in the mechanism of pathogenesis of GML and the regulation of electro-acupuncture, including 15 in medulla and 10 in cerebral cortex. Metabolic pathway analysis showed that the differential metabolites involved 19 metabolic pathways, which could be divided into energy, neurotransmitters, cells and cell membrane and antioxidation according to their functions. The correlation analysis of stomach, medulla and cerebral cortex shows that the stimulation signal of GML may reach the cerebral cortex from the stomach through medulla, and electro-acupuncture can treat GML by regulating the central nervous system (CNS). CONCLUSIONS: 4 days electro-acupuncture treatment can significantly improve gastric mucosal injury, and the curative effect tends to be stable in 7 days treatment. Meanwhile, the pathogenesis of GML and the efficacy of electro-acupuncture involve metabolic pathways such as energy, neurotransmitters, cells and antioxidation, and electro-acupuncture can treat GML by regulating CNS.
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Ovarian cancer (OC) is the most lethal gynecological malignancy, in which chemoresistance is a crucial factor leading to the poor prognosis. Recently, immunotherapy has brought new light for the treatment of solid tumors. Hence, as a kind of immunologically active cancer, it is reasonably necessary to explore the potential mechanism between immune characteristics and cisplatin resistance in OC. Our study focused on the important role of cisplatin resistance-related lncRNAs on mediating the OC tumor immune microenvironment (TIME) using an integrative analysis based on the Cancer Genome Atlas (TCGA) database. First, the cisplatin resistance-related differentially expressed lncRNAs (DELs) and mRNAs (DEMs) were preliminarily screened to construct a DEL-DEM co-expression network. Next, the protein-protein interaction (PPI) network and pivot analysis were performed to reveal the relevance of these lncRNAs with tumor immune response. Second, the novel lncRNA CTD-2288O8.1 was identified as a key gene for the OC cisplatin resistance formation by qRT-PCR and survival analysis. Gain- and loss-of-function assays (Cell Counting Kit-8 (CCK-8) assay, wound-healing scratch assay, transwell assay, and colony formation assay) further verified the activity of CTD-2288O8.1 in OC progression as well. Third, gene set enrichment analysis (GSEA) was applied along with the correlation analyses of CTD-2288O8.1 with ImmuneScore, tumor-infiltrating immune cells (TICs), and immune inhibitory checkpoint molecules, illustrating that CTD-2288O8.1 was strongly associated with the TIME and has the potential to predict the effect of OC immunotherapy. In addition, basic experiments demonstrated that the expression of CTD-2288O8.1 impacted the EGFR/AKT signal pathway activity of OC tumor cells. Of greater significance, it promoted the M2 polarization of macrophage, which is a type of the most important components of the TIME in solid tumor. Taking together, our study revealed cisplatin resistance-related lncRNAs closely linked with tumor immunity in OC, underscoring the potential mechanism of the TIME in conferring cisplatin resistance, which provided the research basis for further clinical treatment. CTD-2288O8.1 was identified to mediate cisplatin resistance and affect the response of immunotherapy, which could serve as a promising biomarker for guiding clinical treatment and improving prognosis in OC.
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BACKGROUND: Moxibustion is increasingly used for treatment of irritable bowel syndrome (IBS). This study investigated the long-term effects of moxibustion for IBS with diarrhea (IBS-D). METHODS: Patients with IBS-D were assigned to receive moxibustion or sham moxibustion (52 each, 3× per week, 6 weeks) and were followed up to 24 weeks. The acupoints were bilateral ST25 and ST36, body surface temperatures at acupoints were 43°C ± 1°C and 37°C ± 1°C for the moxibustion and sham groups, respectively. Primary outcome was changes in IBS Adequate Relief (IBS-AR) from baseline to 6 weeks. Secondary outcomes included the following: IBS symptom severity scale (IBS-SSS), Bristol stool form scale (BSS), IBS quality of life (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). RESULTS: Based on an intention-to-treat analysis, the rate of IBS-AR in the moxibustion group was significantly higher than the sham group at 6 weeks (76.9% versus 42.3%; p < 0.001); the mean decrease of total IBS-BSS score in the moxibustion group was lower than that of the sham group (-116.9 versus -61.5; p < 0.001), both of which maintained throughout the follow-up period. Five specific domains of the IBS-SSS were lower in the moxibustion group than the sham, throughout (p < 0.001). At week 6, the rate of reduction >50 points in IBS-SSS of the treatment group was significantly higher than that of the sham (p < 0.001), which persisted throughout the follow-up period. Similar long-lasting improvements were observed in BSS, stool frequency, and stool urgency (p < 0.001). Improvements of IBS-QOL and HADS were comparable between the groups. CONCLUSIONS: Moxibustion treatment benefits the long-term relief of symptoms in IBS-D patients. TRIAL REGISTRATION: Clinical trials.gov (NCT02421627). Registered on 20 April 2015.
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BACKGROUND AND AIMS: Intestinal fibrosis is one of the severe and common complications of Crohn's disease (CD), but the etiology and pathogenesis remain uncertain. The study intended to examine whether the effect of herb-partitioned moxibustion on rats with CD-associated intestinal fibrosis is associated with the RhoA/ROCK1/MLC pathway. METHODS: All experimental rats were randomly allocated into the normal control group (NC), model control group (MC), and herb-partitioned moxibustion group (HPM). Intestinal fibrosis was established in rats with CD by repeated rectal administrations of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Herb-partitioned moxibustion was applied at the Qihai (CV6) and Tianshu (ST25) acupoints once daily for 10 days in the HPM group. In this study, histological changes were examined by hematoxylin and eosin (HE) staining; then, Masson's trichrome staining was used to assess the degree of fibrosis in each group. Experimental methods of immunohistochemistry, western blotting, and real-time PCR were applied to detect the levels of α-SMA, collagen III, RhoA, ROCK1, and p-MLC. Moreover, the double immunofluorescent staining for the colocalization of both α-SMA and ROCK1 was performed. RESULTS: Contrasted with the normal controls, the collagen deposition and fibrosis scores were increased in colonic tissue of model rats, and HPM decreased the collagen deposition and fibrosis scores. The protein of α-SMA and collagen III in the MC group exceeds that of the NC group; HPM decreased the expression of α-SMA and collagen III in rats with intestinal fibrosis. Similarly, the expression of RhoA, ROCK1, and p-MLC in model rats was obviously increased compared with normal controls; the expression of RhoA, ROCK1, and p-MLC was decreased after HPM. The coexpression of α-SMA and ROCK1 in rats with intestinal fibrosis was higher than normal rats. CONCLUSION: HPM improves CD-associated intestinal fibrosis by suppressing the RhoA/ROCK1/MLC pathway.