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HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R1 and R3 groups. The most potent and selective TAR RNA binder was a3 with R1 = OH, R2 = H and R3 = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules.
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Complejos de Coordinación , Transcriptasa Inversa del VIH , VIH-1 , ARN Viral , Inhibidores de la Transcriptasa Inversa , Rutenio , Rutenio/química , VIH-1/efectos de los fármacos , VIH-1/enzimología , Humanos , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Transcriptasa Inversa del VIH/química , Relación Estructura-Actividad , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , ARN Viral/metabolismo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/química , Duplicado del Terminal Largo de VIH/efectos de los fármacosRESUMEN
To investigate the effect of CPPU (forchlorfenuron) on optical properties of strawberry during growth, the optical properties (absorption coefficient (µa) and reduced scattering coefficient (µs')) of strawberry treated with CPPU solutions at different concentrations (0, 2.5, 5.0 and 7.5 mg/L) were measured in white, color turning and red stages by using a single integrating sphere system over near-infrared wavelength range of 900-1700 nm. The physicochemical properties, i.e., single fruit weight, soluble solids content, firmness and moisture content, as well as microstructure of strawberry were also investigated. The results showed that in white stage, the µa of strawberry treated with 7.5 mg/L CPPU was significantly (p ≤ 0.05) lower than that of untreated strawberry at absorption peak of 1411 nm. In color turning stage, the µs' of strawberry treated with 5 mg/L CPPU was significantly lower than that of treated with 2.5 mg/L at absorption peaks of 975, 1197 and 1411 nm. In red stage, the µa of strawberry treated with 2.5 mg/L CPPU was significantly (p ≤ 0.05) different from that of treated with 7.5 mg/L at 1197 nm. The study indicates that the optical properties of strawberry were affected by CPPU, and it provides useful information for identifying CPPU treated strawberry.
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As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the replication and transmission of the virus. Non-nucleoside RT inhibitors (NNRTIs) block the function of RT by binding to the RNA binding site on RT, with very few targeting viral RNA. In this study, by transforming planar conjugated ligands into a spiro structure, we convert classical Ru(II) DNA intercalators into a nonintercalator. This enables selective binding to HIV-1 transactivation response (TAR) RNA on the outer side of nucleic acids through dual interactions involving hydrogen bonds and electrostatic attraction, effectively inhibiting HIV-1 RT and serving as a selective fluorescence probe for TAR RNA.
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Transcriptasa Inversa del VIH , VIH-1 , Inhibidores de la Transcriptasa Inversa , Rutenio , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/metabolismo , Ligandos , VIH-1/enzimología , VIH-1/efectos de los fármacos , Rutenio/química , Rutenio/farmacología , ARN Viral/metabolismo , ARN Viral/química , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Compuestos de Espiro/metabolismo , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , Estructura Molecular , Humanos , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Duplicado del Terminal Largo de VIH , Sitios de UniónRESUMEN
Evodiamine (EVO), a natural bioactive compound extracted from Evodia rutaecarpa, shows therapeutic ability against malignant melanoma. However, the poor solubility and bioavailability of EVO limit its clinical application. Metal-organic frameworks (MOFs) have shown excellent physical and chemical properties and are widely used as drug delivery systems. Among them, zeolitic imidazolate framework-8 (ZIF-8) is a research popular material because of its unique properties, such as hydrothermal stability, non-toxicity, biocompatibility, and pH sensitivity. In this study, in order to load EVO, a drug carrier that hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) is synthesized. This drug carrier has shown drug loading with 6.2 ± 0.6%, and the nano drugs (EVO@ZIF-8/HA) have good dispersibility. Owing to the decoration HA of EVO@ZIF-8, the potential of the nano drugs is reversed from the positive charge to the negative charge, which is beneficial to blood circulation in vivo. Furthermore, because the CD44-expressing in tumor cells is excessed, the endocytosis and accumulation of nano drugs in tumor cells are beneficial to improvement. Compared with free EVO, EVO@ZIF-8/HA has shown a significantly improved anti-tumor efficacy in vitro and in vivo. In summary, the drug carrier effectively addresses the challenges that are caused by the strong hydrophobicity and low bioavailability of EVO, thereby targeted tumor therapy of EVO can be achieved.
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INTRODUCTION: Chemoimmunotherapy, which benefits from the combination of chemotherapy and immunotherapy, has emerged as a promising strategy in cancer treatment. However, effectively inducing a robust immune response remains challenging due to the limited responsiveness across patients. Endoplasmic reticulum (ER) stress is essential for activating intracellular signaling pathways associated with immunogenic cell death (ICD), targeting drugs to ER might enhance ER stress and improve ICD-related immunotherapy. OBJECTIVES: To improve the immune response of Chemoimmunotherapy. METHODS: ER targeting nanoparticles TSE-CEL/NP were constructed to enhance immunogenic cancer cell death. Flow cytometry, confocal microscope, TEM and immunofluorescence were used to evaluate the ER targeting effect and immunogenic tumor cell death in vitro on B16F10 tumor cells. Unilateral and bilateral tumor models were constructed to investigate the efficacy of anti-tumor and immunotherapy in vivo. Lung metastasis B16F10 melanoma tumor-bearing mice were used to assess the anti-metastasis efficacy. RESULTS: TSE-CEL/NP could specially accumulate in ER, thereby induce ER stress. High ER stress trigger the exposure of CRT, the extracellular release of HMGB1 and ATP. These danger signals subsequently promote the recruitment and maturation of dendritic cells (DCs), which in turn increase the proliferation of cytotoxic T lymphocytes (CD8+ T cells), ultimately resulted in an improved immunotherapy efficacy against melanoma. Invivo experiments showed that TSE-CEL/NP exhibits excellent antitumor efficacy and triggers a strong immune response. CONCLUSION: Our findings demonstrated that celastrol ER targeting delivery could amplify immunogenic cell death in melanoma, which provide experimental basis for melanoma immunotherapy.
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Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.
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Carga Global de Enfermedades , Infecciones por VIH , Humanos , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Infecciones por VIH/epidemiología , Infecciones por VIH/mortalidad , Masculino , Femenino , Anciano , Carga Global de Enfermedades/tendencias , Asia/epidemiología , Estudios de Cohortes , Incidencia , Años de Vida Ajustados por Discapacidad , Costo de EnfermedadRESUMEN
As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.
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Biomarcadores , Espectrometría de Masas , Metabolómica , Metabolómica/métodos , Humanos , Biomarcadores/metabolismo , Espectrometría de Masas/métodos , Descubrimiento de Drogas/métodos , Metaboloma , AnimalesRESUMEN
The reuse and development of natural waste resources is a hotspots and challenges in the research of new fiber materials and the resolution of environmental concern globally. Herein, this study aimed to develop a simple and direct manual extraction process to extract Musa core fibers (MCFs) for rapid water conduction and evaporation. Through simple processes such as ring cutting and stretching, this green and non-destructive inside-out extraction strategy enabled Musa fibers to be naturally and harmlessly degummed from natural Musa stems, with good maintenance of the fiber structure and highly helical morphology. The extracted fibers are composed of regularly and closely arranged cellulose nanofibrils in the shape of ribbon spirally arranged multi-filaments, and the single filament is about 2.65 µm. The high-purity fibers exhibit ultra-high tensile strength under a non-destructive extraction process, and the ultimate tensile strength in dry state is as high as 742.95 MPa. The tensile strength is affected by the number of fiber bundles, which shows that tensile strength and tensile modulus is higher than those of vascular bundle fibers in dry or wet condition. In addition, the MCFs membrane indicates good water conductivity, with a water absorption height of 50 mm for the sample in only 60 s. Moreover, the water evaporation rate of MCFs reaches 1.37 kg m-2 h-1 in 30 min, which shows that MCFs have excellent water conductivity and evaporation rate compared with ordinary cotton fibers. These results indicate that MCFs have great potential in replacing the use of chemical methods to extract fibers from vascular bundles, providing an effective way to achieve sustainability in quick-drying applications, as well as in the sustainable development of natural waste resources.
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Musa , Resistencia a la Tracción , Agua , Agua/química , Musa/química , Celulosa/química , Nanofibras/químicaRESUMEN
OBJECTIVES: To observe the therapeutic efficacy of acupuncture and its effects on abdominal circumference, separation distance of rectus abdominis and quality of life in patients with postpartum diastasis recti abdominis on the basis of diastasis recti abdominis exercise. METHODS: A total of 87 postpartum women with diastasis recti abdominis were randomly divided into an observation group (44 cases) and a control group (43 cases) . The control group was treated with conventional diastasis recti abdominis rehabilitation exercise, including abdominal breathing training and supine leg lifting training, 3 times a day for 2 weeks. On the basis of the treatment in the control group, the observation group was treated with acupuncture at Zhongwan(CV 12), Qihai(CV 6)and bilateral Shenshu(BL 23), Daimai(GB 26), Daheng(SP 15), Zusanli (ST 36), etc., 30 min each time, once a day for 2 weeks. Before and after treatment, the separation distance of rectus abdominis, low back pain visual analogue scale (VAS) score, abdominal circumference and 36-item short form health survey questionnaire (SF-36) score in the two groups were compared, and the clinical effect was evaluated. RESULTS: After treatment, the separation distance of rectus abdominis, low back pain VAS scores, abdominal circumference of the two groups were lower than those before treatment(P<0.05), and the physiological function, physiological role, pain, mental health, emotional role, social function, energy, general health scores and total scores of SF-36 were higher than those before treatment(P<0.05); the separation distance of rectus abdominis, low back pain VAS score, abdominal circumference of the observation group were lower than those in the control group(P<0.05), the sub-item scores and total score of SF-36 of the observation group were higher than those in the control group(P<0.05).The effective rate of the observation group was 95.5% (42/44), which was higher than 79.1% (34/43) in the control group(P<0.05). CONCLUSIONS: Acupuncture combined with diastasis recti abdominis exercise can effectively relieve the low back pain of postpartum diastasis recti abdominis patients, promote the recovery of recti abdominis function, and improve the quality of life. The clinical effect is superior to diastasis recti abdominis exercise alone.
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Terapia por Acupuntura , Diástasis Muscular , Dolor de la Región Lumbar , Femenino , Humanos , Recto del Abdomen , Calidad de Vida , Periodo Posparto , Diástasis Muscular/terapiaRESUMEN
Population structure and lifestyles may have contributed to the epidemiological status of Chronic Kidney Disease due to Type 2 Diabetes (CKD-T2D). This study is a secondary data analysis. Using data from the Global Burden of Disease Study, we describe the changes in CKD-T2D burden and its influencing factors in the population aged 20-59 years from 1990 to 2019. Globally, the incidence, death, and Disability Adjusted Life Years (DALYs) rate of CKD-T2D showed an upward trend and increased with age, and the burden in males was higher than that in females. Population growth and aging were important driving factors for the increase of CKD-T2D DALY burden, while high systolic blood pressure and high body-mass index were the primary attributable risk factors. High body-mass index exhibited higher contributions to high Socioeconomic Development Index (SDI) countries, whereas low SDI countries were more impacted by high systolic blood pressure. The population attributable fraction of CKD-T2D DALY caused by high body-mass index was positively correlated with SDI, while high temperature and lead exposure were negatively correlated. Therefore, strengthening disease screening for people aged 20-59 years and formulating early intervention measures based on the level of socioeconomic development may effectively alleviate the burden of CKD-T2D.
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Diabetes Mellitus Tipo 2 , Personas con Discapacidad , Insuficiencia Renal Crónica , Masculino , Femenino , Adulto , Humanos , Años de Vida Ajustados por Calidad de Vida , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Carga Global de Enfermedades , Factores de Riesgo , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Salud GlobalRESUMEN
Background: Staphylococcus aureus (S. aureus) is the most common causative agent of burn wound infection, that often leads to high morbidity and mortality. However, there is not enough knowledge about the molecular epidemiology and antimicrobial susceptibility of S. aureus isolates from burn wound infections in Fujian, China. Methods: Between 2016 and 2021, 90 S. aureus isolates were collected from burn wound infections in Fujian, China, including 59 methicillin-resistant (MRSA) strains and 31 methicillin-susceptible (MSSA) strains. These were investigated for molecular characteristics, virulence genes, biofilms, and antimicrobial susceptibility. All the isolates were genotyped by multilocus sequence typing (MLST), spa typing, agr typing, and SCCmec typing. Conventional PCR was performed for the detection of virulence genes. Biofilm formation capacity was assessed by tissue culture plate assay (TCP). The antimicrobial susceptibility of the isolates was evaluated using the dilution method. Results: In total, 37 sequence types (ST) and 34 Staphylococcal protein A (spa) types (including a new type named spa-t20720) were identified based on multilocus sequence typing (MLST) and spa typing, respectively. CC8-ST239-t030-agrI-SCCmecIII (57.6%,34/59) and CC7-ST7-t091-agrI (16.1%, 5/31) represented the main clone of MRSA and MSSA isolates, respectively. Antibiotic susceptibility testing identified a significant difference in resistance rates between ST239 and non-ST239 isolates (p < 0.05). Twelve virulence genes were detected, of which the most common were icaA and icaD (both 100%), followed by icaB and icaC (both 96.7%), icaR (95.6%), lukED (81.1%), lukAB (62.2%), pvl (50%), hlgBC (26.7%), and eta (4.4%). Moreover, lukAB, hlgBC, agrI, and agrIII were significantly correlated with burn severity (p < 0.05). MRSA isolates were less likely, compared with MSSA isolates, to carry pvl, lukAB, and hlgBC (p < 0.05). A new spa type, t20720, was identified that contains pvl, lukED, lukAB, hlgBC, icaA, icaB, icaC, icaD, and icaR genes and has strong biofilm formation ability. Conclusion: CC8-ST239-t030-agrI-SCCmecIII and CC7-ST-7-t091-agrI were the prevalent molecular signatures of MRSA and MSSA isolates from burn wound infections in Fujian, China, respectively. The newly identified spa-t20720 isolate, which carries a wide range of virulence genes and has strong biofilm formation ability, requires special clinical attention.
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Methods: Rat models of DN were established using streptozotocin (STZ). The primary metabolic parameters were assessed. The pathological changes of the rat kidney were investigated, and RNA sequencing was performed for each group. Renal tissue apoptosis was detected using the TUNEL assay. In rats and high glucose- (Hg-) induced HK-2 cells, RT-qPCR and western blot were used to analyze the expression of related genes and proteins. Hg medium was used to establish the diabetic kidney environment. The CCK-8 assay and flow cytometry were used to assess cell viability and apoptosis, respectively. Transmission electron microscopy was used to evaluate autophagy in vitro. Results: CRT treatment significantly reduced albuminuria and renal tissue damage in DN rats. Furthermore, CRT administration inhibited apoptosis and promoted autophagy in DN rat kidney tissues. CRT downregulated CD36 expression and activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in DN rat kidney tissues. CRT intervention inhibited Hg-induced apoptosis and reversed autophagy in HK-2 cells. Moreover, overexpression of CD36 suppressed the beneficial effects of CRT. Conclusions: Our study is the first to report that CRT inhibited apoptosis and promoted autophagy in vivo and in vitro, which was achieved by reducing CD36 expression and activating the AMPK pathway. Therefore, CRT may be an effective drug to treat DN.
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Diabetes Mellitus , Nefropatías Diabéticas , Mercurio , Animales , Ratas , Nefropatías Diabéticas/genética , Proteínas Quinasas Activadas por AMP , Apoptosis , Autofagia , Antígenos CD36/genéticaRESUMEN
The monocentric camera based on fiber relay imaging offers benefits of light weight, compact size envelope, vast field of view, and high resolution, which can fully fulfill the index requirements of space-based surveillance systems. However, the fiber optic plate's (FOP) defects will result in the loss of imaging data, and the FOP's discrete structural features will exacerbate the imaging's non-uniformity. A global defect detection approach based on manual threshold segmentation of saturated frames is suggested to detect FOP defect features. The suggested method's efficacy and accuracy are confirmed when compared to the classical Otsu algorithm. Additionally, through tests, the relative imaging response coefficients of each pixel are identified, the response non-uniformity of the pixels is corrected, and the whole image non-uniformity drops from 10.01% to 0.78%. The study in this paper expedites the use of fiber relay imaging-based monocentric cameras in the field of space-based surveillance, and the technique described in this paper is also appropriate for large-array optical fiber coupled relay image transmission systems.
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BACKGROUND: Cancer is the world's leading cause of death and a key hindrance to extending life expectancy. Celastrol, a bioactive compound derived from Tripterygium wilfordii, has been shown to have excellent antitumor activity, but its poor solubility and severe organ toxicity side effects have hampered its clinical application. METHODS: In this study, a self-assembled nanodrug (PLC-NP) was designed to deliver celastrol to tumor sites while efficiently reducing its side effects by conjugating celastrol with the bioactive material LMWH and P-selectin targeting peptide (PSN). Extensive in vitro and in vivo experiments were performed to investigate both therapeutic efficacy and adverse effects. Furthermore, the specific mechanism of the antitumor activity has also been explored. FINDING: The PLC-NP nanodrugs were spherical in shape, with a mean particle size of 115.83 ± 6.93 nm. PLC-NP was sufficiently stable during blood circulation, with a selective target to P-selectin-highly expressed tumor cells, followed by releasing the containing celastrol under acidic environment and high levels of esterase in tumor cells. Both in vitro and in vivo results confirmed that celastrol's antitumor and anti-metastatic abilities were not attenuated and were actually strengthened after being formed into nanodrugs. More importantly, the organ toxicities of the modified celastrol nanodrug were dramatically reduced. Mechanistic study indicated that the inactivation of PI3K/Akt/mTOR signaling pathway and ROS-mediated mitochondrial dysfunction play critical roles in celastrol-mediated autophagy and apoptosis. INTERPRETATION: Our findings could offer a potential strategy for the translation of toxic compounds into clinical therapeutic nanomedicine. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Nanopartículas , Neoplasias , Triterpenos , Humanos , Triterpenos/farmacología , Selectina-P , Fosfatidilinositol 3-Quinasas/metabolismo , Heparina de Bajo-Peso-Molecular/farmacología , Neoplasias/tratamiento farmacológico , Nanopartículas/uso terapéutico , ApoptosisRESUMEN
BACKGROUND: Alzheimer's disease (AD) is a type of disease frequently occurs in the elderly population. Diagnosis and treatment methods for this disease are still lacking, and more research is required. In addition, little is known about the function of the circular RNAs (circRNAs) in AD. METHODS: In this research, RNA expression data of AD from the Gene Expression Omnibus (GEO) database were downloaded. The expression levels of circRNAs in cerebrospinal fluid samples of healthy participants and AD patients were measured by reverse transcriptionquantitative PCR (RT-qPCR). The diagnosed value of differential expressed circRNAs was analyzed with the Receiver operating characteristic curve (ROC). Pathways related to circ_0001535 were found using gene set enrichment analysis (GSEA) and Metascape. The direct interactions between circ_0001535 and E2F transcription factor 1 (E2F1) or E2F1 and dihydrofolate reductase (DHFR) were verified using Chromatin immunoprecipitation (ChIP) and RNA Binding Protein Immunoprecipitation (RIP) assays. Cell Counting Kit-8 (CCK8) and flow cytometry were used to identify the function of circ_0001535/E2F1/DHFR axis on the proliferation and apoptosis of AD cells. RESULTS: In total, 12 circRNAs have been linked to AD diagnosis. The expression levels of 7 circRNAs differed between AD patients and control groups. Circ_0001535 had the most diagnose value among these circRNAs. Hence, circ_0001535 was regarded as a key circRNA in the present study. E2F1/DHFR axis was predicted to be regulated by circ_0001535. In addition, IP assays experiment results showed that E2F1 could bind to the promoter region of DHFR and be regulated by circ_0001535. In vitro results showed that circ_0001535 overexpression could promote DHFR expression, while E2F1 knock down could inhibit DHFR expression in SH-SY5Y cells. Finally, rescue experiments suggested that circ_0001535 could reduce Aß25-35-induced SH-SY5Y cell proliferation and facilitate apoptosis through E2F1/DHFR axis. CONCLUSIONS: Our research in AD circRNA can offer important information regarding the role of specific circRNAs in the AD environment and point to specific future areas of therapeutic intervention in AD.
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Enfermedad de Alzheimer , Neuroblastoma , Anciano , Humanos , ARN Circular/genética , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Proliferación Celular/genética , Biología ComputacionalAsunto(s)
Osteoporosis , Fracturas Osteoporóticas , Humanos , Osteoporosis/complicaciones , Densidad ÓseaRESUMEN
Ferroptosis, an emerging form of regulated programmed cell death, has garnered significant attention in the past decade. It is characterized by the accumulation of lipid peroxides and subsequent damage to cellular membranes, which is dependent on iron. Ferroptosis has been implicated in the pathogenesis of various diseases, including tumors and diabetes mellitus. Traditional Chinese medicine (TCM) has unique advantages in preventing and treating type 2 diabetes mellitus (T2DM) due to its anti-inflammatory, antioxidant, immunomodulatory, and intestinal flora-regulating functions. Recent studies have determined that TCM may exert therapeutic effects on T2DM and its complications by modulating the ferroptosis-related pathways. Therefore, a comprehensive and systematic understanding of the role of ferroptosis in the pathogenesis and TCM treatment of T2DM is of great significance for developing therapeutic drugs for T2DM and enriching the spectrum of effective T2DM treatment with TCM. In this review, we review the concept, mechanism, and regulatory pathways of ferroptosis and the ferroptosis mechanism of action involved in the development of T2DM. Also, we develop a search strategy, establish strict inclusion and exclusion criteria, and summarize and analyze the application of the ferroptosis mechanism in TCM studies related to T2DM and its complications. Finally, we discuss the shortcomings of current studies and propose a future research focus.
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Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy with diverse histological types. This study aimed to detect neoantigens in ccRCC to develop mRNA vaccines and distinguish between ccRCC immunological subtypes for construction of an immune landscape to select patients suitable for vaccination. Using The Cancer Genome Atlas SpliceSeq database, The Cancer Genome Atlas, and the International Cancer Genome Consortium cohorts, we comprehensively analysed potential tumour antigens of ccRCC associated with aberrant alternative splicing, somatic mutation, nonsense-mediated mRNA decay factors, antigen-presenting cells, and overall survival. Immune subtypes (C1/C2) and nine immune gene modules of ccRCC were identified by consistency clustering and weighted correlation network analysis. The immune landscape as well as molecular and cellular characteristics of immunotypes were assessed. Rho-guanine nucleotide exchange factor 3 (ARHGEF3) was identified as a new ccRCC antigen for development of an mRNA vaccine. A higher tumour mutation burden, differential expression of immune checkpoints, and immunogenic cell death were observed in cases with the C2 immunotype. Cellular characteristics increased the complexity of the immune environment, and worse outcomes were observed in ccRCC cases with the C2 immunotype. We constructed the immune landscape for selecting patients with the C2 immunotype suitable for vaccination.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Selección de Paciente , Vacunas Sintéticas , ARN Mensajero/genética , Neoplasias Renales/genética , Vacunas de ARNmRESUMEN
Weizhi Xun and Changwang Wu contributed equally to this work In October 2020, bayberry (Myrica rubra (Lour.) S. et Zucc.) leaves that beginning to wither were collected in Wencheng County (N27°50', E120°03'). In the county, 4,120 ha of bayberry were planted, of which 58% were affected by the disease, and the severity of leaf disease per plant was 5 to25%. Bayberry leaves leaves were intensely green at first, then gradually turned yellow and brown,and completely withered. The leaves did not fall off at the beginning of the symptoms, but did fall after 1 to 2 months. To identify the pathogen, 50 diseased leaves with typical symptoms were collected from 10 diseased trees. Leaves with necrotic-tissue were firstly washed with sterilized water, and then tissue at the disease-/ healthy-tissuejunction removed with sterile surgical scissors. The tissues were soaked in 75% ethanol for 30 s, followed by 5% sodium hypochlorite solution for 3 to 4 min, rinsed with sterilized water 4 times, and placed on sterilized filter paper. The tissue was placed on PDA medium and cultured in an incubator at 25â (Nouri et al. 2019). After the colonies grew around the tissue, mycelia with the same morphology was selected and placed on fresh PDA. A pure culture of the pathogen was obtained after repeating the last process several times. The isolatedcolonies were white, with a round edge and a light-yellow back. Conidia were straight or slightly curved, with 3 to 4 septations. The internal transcribed spacer (ITS) regin translation elongation factor 1-α gene (TEF1-α), and beta-tubulin gene (ß-TUB)(Chaiwan et al. 2020; Li et al. 2021; Chen et al. 2020; Chen et al. 2018) of the two strains were amplified and sequenced, and the sequences were uploaded to Gen bank (GenBank accession number.ACCC 35162: ITS OP891011, TEF1-α OP903533, ß-TUB OP903531; ACCC 35163: ITS OP891012, ß-TUB OP903534, TEF1-α OP903532). BLAST alignment indicated that the ITS sequence of strain ACCC 35162 had 100% identity with NR_147549.1, the TEF sequence had 100% identity with MT552449.1, and the TUB sequence had 99.87% identity with KX895323.1; the ITS sequence of strain ACCC 35163 had 100% identity with NR_147549.1, the TEF sequence had 100% identity with MT552449.1, and the TUB sequence had 99.86% identity with KX895323.1. A Phylogenetic tree using maximum likelihood/rapid bootstrapping run on XSEDE based on the above three sequences inferred that the two strains were identical to P. kenyana (Miller et al. 2010). The strain was preserved in the Agricultural Culture Collection of China (Preservation numbers: ACCC 35162, ACCC 35163). Following Koch's rule, six healthy plants leaves were inoculated with conidial suspensions (106 conidia mL-1) and mycelial plugs (5 mm)ï¼and then placed in an artificial climate chamber (25â, 90% humidity, 16-h light), sterile PDA and sterile water were used as blank controls. The same treatment was applied to fresh bayberry leaves under laboratory conditions, and brown spots were observed after three days. There were no symptoms in the control group. The experimental symptoms were similar to those in the field. Using the previous method, the same fungus was reisolated from the diseased leaves and again identified as P. kenyana. As far as we know, this is the first report causing disease on P. kenyana infecting bayberry in China, this disease seriously affected the yield and quality of bayberry and caused economic losses to farmers.
RESUMEN
Negativity bias refers to the phenomenon whereby people put more weight on negative information. Although evolutionarily favorable for survival, negative bias in impression processing is detrimental to relationships and cooperation. To explore whether the motivation to maintain relationships, indicated by self-construal, mitigates negativity bias, two studies were conducted. In study 1, participants interacted with three agents (worsened, improved, baseline) in a modified social learning task and evaluated the moral level of these agents. Results showed that positivity bias appeared among interdependent individuals, with larger updating for the improved agent than for the worsened agent. Moreover, interdependent individuals exhibited less immediate decreases toward the worsened agent and steeper increases toward the improved agent than did independent individuals. To validate the results of study 1, we used a narrative description paradigm in study 2. Participants read the behavior descriptions of agents and rated them on morality. The negativity bias was significantly mitigated among individuals with high interdependence, though it did not reverse. These results indicate that interdependent individuals focus more on positive information when others change, yielding a more positive pattern in impression updating. This flexible interpersonal coping strategy can bring advantages to social interaction and cooperation.