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1.
Chem Biol Drug Des ; 103(4): e14518, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38570329

RESUMEN

Icariin has shown the potential to treat osteoarthritis (OA), but the specific mechanism still needs further exploration. Therefore, this study attempted to reveal the effect and mechanism of icariin on OA based on in vitro and in vivo experiments. In vivo, a mouse model of OA was established by cutting the anterior cruciate ligament, and 10 mg/kg icariin was given to mice orally. Then, the OA injury and pathological changes of cartilage tissue in mice were identified by OA index and hematoxylin and eosin staining. In vitro, the viability of C28/I2 cells incubated with different concentrations of icariin was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide assay. Subsequently, C28/I2 cells induced by IL-1ß were used as the cell model of OA, the expression of Sirtuin (SIRT)-1 in cells was knocked down, and icariin was added for intervention. Next, western blot was used to observe the expression level of sirtuin 1 (SIRT-1)-Nrf2-heme oxygenase 1 (HO-1) signaling pathway-related proteins in cells of each group. Besides, cell viability and apoptosis were detected by MTT and apoptosis assay, and DNA damage was observed by comet assay. In vivo experiments, intragastric administration of icariin could effectively reduce the OA index of mice, improve the pathological changes of cartilage tissue, and obviously activated the SIRT-1-Nrf2-HO-1 signaling pathway. In vitro experiments, icariin did not exhibit toxic effect on C28/I2 cells, but could activate the SIRT-1-Nrf2-HO-1 signaling pathway, improve the viability, reduce the level of apoptosis and relieve the DNA damage in OA cells; however, these effects were inhibited by si- SIRT-1. Icariin can improve the symptoms of OA by activating the SIRT-1-Nrf2-HO-1 signaling pathway.


Asunto(s)
Condrocitos , Flavonoides , Osteoartritis , Ratones , Animales , Condrocitos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Sirtuina 1/metabolismo , Hemo-Oxigenasa 1/metabolismo , Transducción de Señal , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Apoptosis
2.
Sex Med ; 12(2): qfae020, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38586249

RESUMEN

Background: Penile hypersensitivity is not the whole penis, but rather only a part of the penis. Though local anesthetic can prolong intravaginal ejaculation latency time by reducing penile hypersensitivity, the effect on the hypersensitive and nonsensitive areas of penis is still unclear. Aim: The study aimed to explore whether the effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation. Methods: Penile neurophysiological tests were performed on 290 patients with primary premature ejaculation. The sensory threshold, latency, and amplitude were recorded before and after the topical application of a local anesthetic (lidocaine cream) on the penis. Outcomes: Local anesthetics increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference but only prolonged the latency of the hypersensitive areas. Results: According to the neurophysiological results, 149 of 290 patients with primary premature ejaculation had normal penile sensitivity and 141 had penile hypersensitivity. While penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive, and may be that only a part of the penis is hypersensitive, and we examined the following hypersensitivities: glans hypersensitivity only (14 cases), shaft hypersensitivity only (77 cases), and whole penis hypersensitivity (50 cases). Local anesthetics (lidocaine cream) increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference (P < .001) but only prolonged the latency of the hypersensitive areas (P < .001), and the latency of the nonsensitive areas was not different (P > .05). Clinical Implications: The present discovery implies that it is possible to improve ejaculation by applying local anesthetics externally to the hypersensitive areas of the penis to reduce the afferent local sensory signals, and improve intravaginal ejaculation latency time through accurately decreasing penile sensibility. Strengths & Limitations: This is the first large-sample study to explore the difference of local anesthetics' effects on the hypersensitive and nonsensitive areas of the penis by means of neurophysiological methods in premature ejaculation. Our study exclusively examines alterations in penile evoked potential following electrical stimulation, which may not entirely encompass shifts in penile receptivity during sexual activity. Conclusion: The effects of local anesthetics on the same penis varied with penile sensitivity, and can only prolong the latency of hypersensitive area of the penis. The effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation.

3.
Acta Pharmacol Sin ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689095

RESUMEN

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.

4.
Nat Prod Res ; : 1-7, 2023 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-38008924

RESUMEN

Artemisia annua is an essential aromatic medicinal plant endemic to China. Here, essential oil was extracted from wild A. annua from Ningxia, China. GC-MS analysis showed that A. annua essential oil was dominated by artemisia ketone, a characteristic compound accounting for 31.26%, followed by eucalyptol (14.89%), camphor (8.69%), myrcene (8.25%) and α-pinene (6.65%). The overall antioxidative potential represented by DPPH and ATBS free radical scavenging rates was weak. The essential oil exhibited good bactericidal activities against Escherichia coli and Staphylococcus aureus and fungicidal activities against Trichophyton rubrum and Epidermophyton floccosum. The minimum inhibitory and microbicidal concentrations were 0.02 mg/mL and 5.12 mg/mL for both bacteria, 0.315% and 2.5% for E. floccosum, and 0.625% and 5% for T. rubrum. The results suggest that A. annua essential oil may be an antimicrobial adjuvant to be applied in pharmaceutical and cosmetic industries.

5.
ACS Appl Mater Interfaces ; 15(35): 41457-41465, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37615533

RESUMEN

Li-CO2 batteries that integrate energy storage with greenhouse gas fixation have received a great deal of attention in the pursuit of carbon neutrality. However, cyclic accumulation of the insulative and insoluble Li2CO3 on the cathode surface severely restrains the battery cyclability, especially under a high depth of discharge/charge. Herein, we design and fabricate a microreactor-type catalyst by embedding Ru nanoparticles into the shells of mesoporous hollow carbon spheres. We show that both the hollow cavity and mesoporous shell are indispensable for concertedly furnishing a high activity to catalyze reversible Li2CO3 formation/decomposition. This unique structure ensures that the Ru sites masked by exterior Li2CO3 deposits during charging can resume the redox process of discharge by working with the prestored electrolyte to establish an inner reaction path. The thus fabricated Li-CO2 batteries demonstrate remarkable cyclability of 1085 cycles under 0.5 Ah g-1 and 326 cycles under 2 Ah g-1 at 1 A g-1, outshining most of the literature reports. This study highlights a smart catalyst design to boost the reversibility and cyclability of Li-CO2 batteries through an "in & out" strategy.

6.
Surg Innov ; 30(4): 445-454, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37026616

RESUMEN

BACKGROUND: This study aims to investigate the value of the AngioJet thrombectomy system with adjunct of catheter-directed thrombolysis (CDT) in treating lower extremity deep venous thrombosis (LEDVT). METHODS: 48 patients who were clinically confirmed LEDVT and treated by percutaneous mechanical thrombectomy (PMT) combined with CDT, were included in this retrospective study (AJ-CDT, n = 33; Suction-CDT, n = 15). Baseline characteristics, clinical outcomes and surveillance data were reviewed and analyzed. RESULTS: The overall clot reduction rate of AJ-CDT group was significantly higher than that of Suction-CDT group (77.86% vs 64.47%, P = .027). The CDT therapeutic time (5.75 ± 3.04 vs 7.67 ± 2.82 days, P = .045) and urokinase dosage (3.63 ± 2.16 vs 5.76 ± 2.12 million IU, P = .003) were lower in AJ-CDT group, respectively. There was statistical significance in the transient hemoglobinuria between 2 groups (72.73% vs 6.67%, P < .001). At postoperative 48 hours, the serum creatinine (Scr) value was higher in AJ-CDT group compared to Suction-CDT group statistically (78.56 ± 32.16 vs 60.21 ± 15.72 µmol/l, P = .049). However, the incidence of acute kidney injury (AKI) and uric acid (UA) concentration at postoperative 48 hours between these 2 groups were no statistical difference. There was no statistical significance in the Villalta score and post-thrombosis syndrome (PTS) incidence during postoperative follow-up. CONCLUSIONS: AngioJet thrombectomy system is more effective for the treatment of LEDVT by providing a higher clot reduction rate with shorter thrombolytic time and lower thrombolytic drug dosage. However, the device-related potential risk of renal function injury should be taken appropriate precautions.


Asunto(s)
Terapia Trombolítica , Trombosis de la Vena , Humanos , Terapia Trombolítica/efectos adversos , Estudios Retrospectivos , Succión , Resultado del Tratamiento , Trombectomía/efectos adversos , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/cirugía , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Catéteres , Extremidad Inferior
7.
Int J Behav Nutr Phys Act ; 20(1): 26, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36890553

RESUMEN

BACKGROUND: Accelerometer measures of physical behaviours (physical activity, sedentary behaviour and sleep) in observational studies offer detailed insight into associations with health and disease. Maximising recruitment and accelerometer wear, and minimising data loss remain key challenges. How varying methods used to collect accelerometer data influence data collection outcomes is poorly understood. We examined the influence of accelerometer placement and other methodological factors on participant recruitment, adherence and data loss in observational studies of adult physical behaviours. METHODS: The review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA). Observational studies of adults including accelerometer measurement of physical behaviours were identified using database (MEDLINE (Ovid), Embase, PsychINFO, Health Management Information Consortium, Web of Science, SPORTDiscus and Cumulative Index to Nursing & Allied Health Literature) and supplementary searches to May 2022. Information regarding study design, accelerometer data collection methods and outcomes were extracted for each accelerometer measurement (study wave). Random effects meta-analyses and narrative syntheses were used to examine associations of methodological factors with participant recruitment, adherence and data loss. RESULTS: 123 accelerometer data collection waves were identified from 95 studies (92.5% from high-income countries). In-person distribution of accelerometers was associated with a greater proportion of invited participants consenting to wear an accelerometer (+ 30% [95% CI 18%, 42%] compared to postal distribution), and adhering to minimum wear criteria (+ 15% [4%, 25%]). The proportion of participants meeting minimum wear criteria was higher when accelerometers were worn at the wrist (+ 14% [ 5%, 23%]) compared to waist. Daily wear-time tended to be higher in studies using wrist-worn accelerometers compared to other wear locations. Reporting of information regarding data collection was inconsistent. CONCLUSION: Methodological decisions including accelerometer wear-location and method of distribution may influence important data collection outcomes including recruitment and accelerometer wear-time. Consistent and comprehensive reporting of accelerometer data collection methods and outcomes is needed to support development of future studies and international consortia. Review supported by the British Heart Foundation (SP/F/20/150002) and registered (Prospero CRD42020213465).


Asunto(s)
Acelerometría , Ejercicio Físico , Humanos , Adulto , Recolección de Datos/métodos , Conducta Sedentaria , Proyectos de Investigación
8.
Asian J Androl ; 25(4): 487-491, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36861504

RESUMEN

The penis is a vital organ of perception that transmits perceived signals to ejaculation-related centers. The penis consists of the glans penis and penile shaft, which differ considerably in both histology and innervation. This paper aims to investigate whether the glans penis or the penile shaft is the main source of sensory signals from the penis and whether penile hypersensitivity affects the whole organ or only part of it. The thresholds, latencies, and amplitudes of somatosensory evoked potentials (SSEPs) were recorded in 290 individuals with primary premature ejaculation using the glans penis and penile shaft as the sensory areas. The thresholds, latencies, and amplitudes of SSEPs from the glans penis and penile shaft in patients were significantly different (all P < 0.0001). The latency of the glans penis or penile shaft was shorter than average (indicating hypersensitivity) in 141 (48.6%) cases, of which 50 (35.5%) cases were sensitive in both the glans penis and penile shaft, 14 (9.9%) cases were sensitive in the glans penis only, and 77 (54.6%) cases were sensitive in the penile shaft only (P < 0.0001). There are statistical differences in the signals perceived through the glans penis and the penile shaft. Penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive. We classify penile hypersensitivity into three categories, namely, glans penis, penile shaft, and whole-penis hypersensitivity, and we propose the new concept of penile hypersensitive zone.


Asunto(s)
Eyaculación Prematura , Masculino , Humanos , Eyaculación/fisiología , Pene/inervación , Potenciales Evocados Somatosensoriales/fisiología
9.
Scand J Med Sci Sports ; 33(8): 1384-1398, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36999303

RESUMEN

The associations between different types and contexts of stepping behaviors and cardiometabolic (CM) health markers are unclear. This study aimed to examine the associations of daily total, walking, stair, incidental and purposeful steps with cardiometabolic risk. A total of 943 women (mean age ± SD = 44.1 ± 1.6 years) from the Australian Longitudinal Study on Women's Health (ALSWH) were included in this cross-sectional study. Daily total, walking, stair, incidental, and purposeful steps were measured using thigh-worn accelerometry. Outcomes comprised of CM markers of adiposity, blood pressure, resting heart rate, lipids, glycaemia, and the composite CM score. We used generalized linear modeling and multiple linear regression to assess the associations. We observed that all stepping behaviors were beneficial to CM health, for example, compared to the lowest quartile (Q1), the change of the composite CM score across low to high quartile of purposeful steps was -0.12 (Q2, 95% CI: -0.41, 0.17), -0.16 (Q3, -0.46, 0.14), and -0.36 (Q4, -0.66, -0.05). Stair steps showed linear associations with blood pressure and adiposity biomarkers, for example, the change of quartile of waist circumference was -1.45 cm (Q2, -4.35, 1.44), -3.56 cm (Q3, -6.52, -0.60), and -7.08 cm (Q4, -10.31, -3.86). Peak 30-min walking intensity showed independent association with adiposity biomarkers (p linear < 0.001 and p = 0.002 for waist circumference and BMI, respectively). Our study showed that all stepping forms were beneficial to CM health. Higher stair steps and peak 30-min walking cadence were associated with a steep decline of adiposity biomarkers. Purposeful steps showed more consistent associations with CM biomarkers than incidental steps.


Asunto(s)
Enfermedades Cardiovasculares , Salud de la Mujer , Persona de Mediana Edad , Humanos , Femenino , Estudios Longitudinales , Estudios Transversales , Factores de Riesgo , Australia , Obesidad , Biomarcadores
10.
Immunity ; 56(5): 1027-1045.e8, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-36791722

RESUMEN

Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription factor SMAD4 in microglia and embryonic-derived BAMs using Crybb1-Cre caused a developmental arrest of microglia, which instead acquired a BAM specification signature. By contrast, the development of genuine BAMs remained unaffected. Our results reveal that SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate and highlight Crybb1-Cre as a tool for targeting embryonic brain macrophages.


Asunto(s)
Macrófagos , Microglía , Ratones , Animales , Microglía/metabolismo , Macrófagos/metabolismo , Integrasas/genética , Integrasas/metabolismo , Encéfalo/metabolismo
11.
Artículo en Inglés | MEDLINE | ID: mdl-36758222

RESUMEN

Owing to their structural tunability for furnishing high catalytic activity and photoactivity, perovskite oxides are a class of promising materials for high-performance photocathode catalysts in a photoassisted lithium oxygen battery (LOB), which is still in its infancy. Herein, single-crystalline LaCoO3 (LCO) is successfully synthesized through a microwave-assisted approach and selenylated to simultaneously introduce anionic doping and oxygen vacancies, boosting not only the electrocatalytic activity toward reversible Li2O2 formation/decomposition, but also the photoactivity to further reduce the charge/discharge polarization. As a result, LOBs utilizing Se-doped LCO as the photocathode catalyst demonstrate a superior performance under illumination in all aspects of energy efficiency, specific capacity, and cycling stability, ranking among the best reported in the literature for perovskite oxides. The photoenhanced charge kinetics is found to be correlated with the accelerated Li2O2 nucleation with lowered granule size, which is key to both the improved charge/discharge capacity and reversibility. The results underscore the tailoring of perovskite structure to aggrandize both the catalytic activity and photoactivity for concertedly promoting the kinetics of LOBs.

12.
Oncol Rep ; 49(2)2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36633144

RESUMEN

4­Methoxydalbergione (4­MD) can inhibit the progression of certain types of cancer; however, its effects on esophageal cancer (EC) remain unclear. The present study aimed to investigate the inhibitory effect of 4­MD on EC and its molecular mechanism. ECA­109 and KYSE­105 cells were treated with or without lipopolysaccharide (LPS) and 4­MD. Cell Counting Kit­8 and colony formation assays were used to analyze cell proliferation. Wound healing assay was performed to evaluate cell migration. ELISA and western blotting were performed to measure the expression levels of NF­κB and inflammatory cytokines. In cells treated with 4­MD, proliferation and migration were significantly inhibited, the levels of inflammatory cytokines were downregulated and the NF­κB signaling pathway was inactivated. Notably, proliferation, migration, inflammation and NF­κB were promoted by LPS, whereas 4­MD reversed the increases induced by LPS in EC cells. In conclusion, 4­MD may attenuate the proliferation and migration of EC cells by inactivating the NF­κB signaling pathway.


Asunto(s)
Benzoquinonas , Neoplasias Esofágicas , FN-kappa B , Humanos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Lipopolisacáridos/farmacología , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Benzoquinonas/farmacología
13.
Int J Biol Macromol ; 229: 146-157, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36528149

RESUMEN

Developing nerve conduits with biological cues is a promising approach for repairing peripheral nerve injuries. Although most biological cues incorporated into conduits generally exert their biological functions at the surface, they could not be released into the on-demand regeneration sites under physiological conditions. Herein, we firstly report a bio-orthogonally functionalized chitosan scaffold with esterase-activatable release for peripheral nerve regeneration. In this study, biological cues are not only selectively conjugated into nerve conduits by bio-orthogonal reaction, but also precisely released in on-demand regeneration sites via esterase-activatable cleavage for peripheral nerve repair. Moreover, this nerve scaffold with esterase-activatable release could promote Schwann cells proliferation. In a rat sciatic nerve defect model, the bio-orthogonally functionalized scaffold with esterase-activatable release significantly increased sciatic nerve function recovery and improved target muscles weight. This strategy of incorporating esterase-activatable bioactive cues into peripheral nerve conduits offers great potential in preclinical studies.


Asunto(s)
Quitosano , Tejido Nervioso , Traumatismos de los Nervios Periféricos , Ratas , Animales , Nervio Ciático/fisiología , Traumatismos de los Nervios Periféricos/terapia , Regeneración Nerviosa , Células de Schwann
14.
Artículo en Inglés | MEDLINE | ID: mdl-36471694

RESUMEN

Premature ovarian failure (POF) is characterized by hormonal disorders, amenorrhea, and premature loss of fertility potential in women of reproductive age. Several studies have been conducted on the effectiveness of traditional Chinese medicine (TCM) in treating POF. TCM relied primarily on apoptosis, immunity, and aging to treat POF based on the studies of domestic and foreign literature. Zuogui pills inhibited mitochondrial-dependent apoptosis in the treatment of POF. Huyang Yangkun formula regulated the downstream of the Bcl-2 family to resist apoptosis through the aquaporin-1 protein. Modified Bazhen decoction regulated apoptosis in POF by regulating X-linked inhibitors of apoptosis protein. Bushen Tianjing recipe was effective in treating POF by promoting angiogenesis and preventing apoptosis. As for immunity, Bushen Jianpi prescription and Er-Xian decoction cured autoimmunity POF models and increased follicular development-related protein expression. Bushen Huoxue Tang improved ovarian function and reduced ovarian inflammation by regulating the Nrf2/Keap1 signaling pathway and T lymphocytes. Taohong Siwu decoction promoted the proliferation and differentiation of granulosa cells of POF mice by regulating the TGF-ß1/Smads signaling pathway. In addition, ginsenoside Rg1 and Jiajian Guisheng formula treated POF by regulating cell aging-related mechanisms. Si Wu Tang treated POF by activating the angiogenesis-related proteins. The goal of this review is to serve as a reference for in-depth research into the treatment of POF with TCM and provide inspiration for new diagnostic methods and treatment options.

15.
Front Immunol ; 13: 927811, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36405685

RESUMEN

Circular RNA (circRNA), a novel class of non-coding RNA, has been reported in various diseases, especially in tumors. However, the key signatures of circRNA-competitive endogenous RNA (ceRNA) network are largely unclear in colorectal cancer (CRC). We first characterized circRNAs profile by using circRNA-seq analysis from real-word dataset. The expression level of hsa_circ_0066351 in CRC tissues and cell lines was detected by quantitative real-time PCR. Then, cell proliferation assay was used to confirm the proliferation function of hsa_circ_0066351. Next, Cytoscape was used to construct circRNA-miRNA-mRNA networks. Last but not least, the landscape of hsa_circ_0066351-miRNA-mRNA in CRC had been investigated in the bulk tissue RNA-Seq level and single-cell Seq level. We proved that hsa_circ_0066351 was significantly downregulated in CRC cell lines and tissues (P < 0.001), and was negatively associated with distant metastasis (P < 0.01). Significantly, the expression of hsa_circ_0066351 was associated with better survival in patients with CRC. Function assays showed that hsa_circ_0066351 could inhibit CRC cells proliferation. In addition, a ceRNA network, including hsa_circ_0066351, two miRNAs, and ten mRNAs, was constructed. Our analyses showed that these ten mRNAs were consistently downregulated in pan-cancer and enriched in tumor suppressive function. A risk score model constructed by these ten downstream genes also indicated that they were related to the prognosis and immune response in CRC. In conclusion, we demonstrated that a novel circRNA (hsa_circ_0066351) inhibited CRC proliferation, and revealed a potential prognostic and immunotherapeutic biomarker in CRC.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , ARN Circular/genética , Pronóstico , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores , ARN Mensajero/genética , ARN Mensajero/metabolismo , Neoplasias Colorrectales/patología , Inmunoterapia
16.
Front Immunol ; 13: 951529, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36159831

RESUMEN

Background: Immunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified. Methods: In this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models. Results: The 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis. Conclusion: In conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Axitinib , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Docetaxel , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunoterapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Pronóstico , Vinblastina
17.
Molecules ; 27(14)2022 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-35889285

RESUMEN

Historical marquisette curtains were composed of lightweight fabrics, woven in an open-mesh and leno-type weave, usually made of silk, and found in Qing imperial buildings. As panel curtains, they were exposed to light, and so underwent fading. This study investigated the manufacturing technology and fading mechanism of dyed marquisette fabric from the Studio of Cleansing Fragrance, the Palace Museum (Beijing). The technological aspects were identified. The types of weave, fiber, and adhesive used to fix the curtain to the wooden frame were identified through microscopic observation and infrared spectroscopy. A color change characterization was performed based on UV-visible diffuse reflectance spectra. The textile colorant was identified as malachite green (MG), and its degradation by light was subsequently studied by dynamic photolysis experiments in a kinetic solution for the rapid exploration of by-products. The main degradation pathways were thus identified and the factors responsible for the induced color changes were discussed. A comparison of the liquid chromatography-mass spectrometry (LC-MS) results of the products derived from the photolysis method as well as of the samples extracted from the object allowed for the identification of the presence of different degradation pathways in the faded and unfaded parts of the textile. A metabolomics analysis was applied to account for the differences in the degradation pathways.


Asunto(s)
Colorantes , Perfumes , Beijing , Colorantes/química , Museos , Odorantes , Colorantes de Rosanilina
18.
Proc Natl Acad Sci U S A ; 119(23): e2204557119, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35653568

RESUMEN

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile.


Asunto(s)
Eosinófilos , Receptores de Hidrocarburo de Aril , Receptores de Superficie Celular , Eosinofilia/terapia , Hipersensibilidad a los Alimentos/terapia , Inmunomodulación , Intestino Delgado , Recuento de Leucocitos , Ligandos , Receptores de Hidrocarburo de Aril/genética
19.
ACS Appl Mater Interfaces ; 14(16): 18561-18569, 2022 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-35417124

RESUMEN

The high activation barrier and sluggish kinetics of Li2CO3 decomposition impose a severe challenge on the development of a Li-CO2 battery with high Coulombic efficiency. To tackle this issue, herein we devise a novel synthetic tactic by combining electrostatic assembly with in situ polycondensation to obtain a single-atomic Ru catalyst of high density up to ∼5 wt %. When deployed to the CO2 cathode, the catalyst delivered an extraordinary capacity of 44.7 Ah g-1, an ultralow charge/discharge polarization of 0.97 V at 0.1 A g-1 (1.90 V at 2 A g-1), and a long-term cycling stability up to 367 cycles at 1 Ah g-1 (196 cycles at 2 Ah g-1), outshining most of the state-of-the-art CO2 cathode catalysts reported today. Further through extensive in situ and ex situ electroanalytical, spectroscopic, and microscopic characterizations, we attribute the superb battery performance mainly to the highly reversible Li2CO3 formation/decomposition, facilitated by the homogenized and downsized Li2CO3 nucleation and growth on account of the high density single-atomic Ru loading. This work not only offers a facile method to fabricate single-atom catalysts with high mass loading but also sheds light on promoting the reversible Li-CO2 reaction by mediating product morphology.

20.
Nat Immunol ; 23(4): 619-631, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35332328

RESUMEN

Innate lymphocytes encompass a diverse array of phenotypic identities with specialized functions. DNA methylation and hydroxymethylation are essential for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes. Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse innate lymphoid cell 3 (ILC3), ILC2 and natural killer (NK) cells. We identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DHMRs) between ILC and NK cell subsets and correlated them with transcriptional signatures. We associated lineage-determining transcription factors (LDTFs) with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions (OCRs), histone modifications and TF-binding sites. We further identified an association between hydroxymethylation and NK cell superenhancers (SEs). Using mice lacking the DNA hydroxymethylase TET2, we showed the requirement for TET2 in optimal production of hallmark cytokines by ILC3s and interleukin-17A (IL-17A) by inflammatory ILC2s. These findings provide a powerful resource for studying innate lymphocyte epigenetic regulation and decode the regulatory logic governing their identity.


Asunto(s)
Metilación de ADN , Inmunidad Innata , Animales , Cromatina/genética , Epigénesis Genética , Inmunidad Innata/genética , Células Asesinas Naturales , Linfocitos , Ratones
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