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1.
JACC Case Rep ; 29(8): 102252, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38774808

RESUMEN

Takayasu arteritis is characterized by blood vessel inflammation involving the aorta and its branches. We describe a patient with Takayasu arteritis with severe multivessel involvement and classic physical examination findings but virtually no symptoms because of the presence of extensive collateral circulation seen on computed tomography angiography and magnetic resonance angiography imaging.

2.
Biol Trace Elem Res ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720017

RESUMEN

Metals are recognized as important factors related to breast cancer (BC) risk. Homologous recombination repair (HRR) genes might modify the toxicity of metals by influencing the distribution and metabolism of metal compounds. This study aims to investigate the modification effects of single nucleotide polymorphisms (SNPs) in HRR genes on the associations between urinary metals and BC risk. A total of 685 BC cases and 741 controls were recruited from October 2009 to December 2012. Twenty-one metals were analyzed in urine samples using inductively coupled plasma mass spectrometry (ICP-MS), and three SNPs (LIG3 rs1052536, RFC1 rs6829064, and RAD54L rs17102086) were genotyped. We identified significant interactions between four metals and two SNPs on the risk of BC. For LIG3 rs1052536 C/T variant, participants with CT/TT genotypes exposed to higher cobalt (Co) levels had higher BC risk compared to those with CC genotype (Pinteraction = 0.048). For RAD54L rs17102086 T/C variant, participants with TT genotype who were exposed to higher levels of zinc (Zn), Co, arsenic (As), and strontium (Sr) had more pronounced BC risk than the CC/TC genotypes (all Pinteraction < 0.05). This study showed compelling evidence for the interaction between genetic variants within the HRR system and urinary metals on BC risk. Our findings highlight the need to consider genetic makeup when evaluating the carcinogenic or protective potential of metals.

3.
J Environ Manage ; 360: 121124, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38733838

RESUMEN

Forests, the ancient wooden giants, are both symbols of natural beauty and reservoirs of carbon stocks. The current climate crisis has created an urgent need for an in-depth study of forest ecosystems and carbon stocks. Based on forest inventory data from field surveys and four bioclimatic zones [Zone 1 (Z1, humid forest), Zone 2 (Z2, semi-humid forest), Zone 3 (Z3, semi-humid to semi-arid forest-grassland), and Zone 4 (Z4, semi-arid typical grassland)], two methods [Method 1 (M1) and Method 2 (M2)] were used to estimate carbon stocks in forest ecosystems in Shaanxi Province, China, and explored the spatial patterns of carbon pools and potential influences. The total forest ecosystem carbon pool amounted to 520.80 Tg C, of which 53.60% was stored aboveground, 17.16% belowground, and 29.24% in soil (depth of 0-10 cm). Spatially, there were marked north-south gradients in both biomass (Z2 > Z3 > Z1 > Z4) and soil organic carbon densities (Z1 > Z2 > Z3 > Z4). The differences between aboveground and belowground biomass carbon density across broadleaf, needle-leaf, and broadleaf and needle-leaf mixed forest were not pronounced, while soil organic carbon density had the order of broadleaf (18.38 Mg C/ha) > needle-leaf (11.29 Mg C/ha) > broadleaf and needle-leaf mixed forest (10.33 Mg C/ha). Under an ideal scenario that excludes external factors, mainly forest growth, the sequestration potential of forest biomass by 2032 was estimated by M1 as 85.43 Tg, and by M2 to be substantially higher at 176.21 Tg. As of 2062, M1 estimated 155.97 Tg of sequestration potential for forest biomass. The spatial patterns of forest biomass and soil carbon density were closely related to climatic factors, and these relationships allowed the spatial division into two distinct climatic regions. Moreover, biomass carbon density was significantly correlated with the normalized difference vegetation index, soil silt, and elevation. This study provides key information for promoting the strategic shift from light-green to deep-green forest systems in Shannxi Province and updates the estimation methods of forest ecosystems' carbon pools based on field surveys.

4.
Toxicol In Vitro ; 98: 105840, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38723977

RESUMEN

Diabetic liver injury (DLI) is a chronic complication of the liver caused by diabetes, and its has become one of the main causes of nonalcoholic fatty liver disease (NAFLD). The gasdermin E (GSDME)-dependent pyroptosis signaling pathway is involved in various physiological and pathological processes; however, its role and mechanism in DLI are still unknown. This study was performed to investigate the role of GSDME-mediated pyroptosis in AML-12 cell injury induced by high glucose and to evaluate the therapeutic potential of caspase-3 inhibition for DLI. The results showed that high glucose activated apoptosis by regulating the apoptotic protein levels including Bax, Bcl-2, and enhanced cleavage of caspase-3 and PARP. Notably, some of the hepatocytes treated with high glucose became swollen, accompanied by GSDME-N generation, indicating that pyroptosis was further induced by active caspase-3. Moreover, the effects of high glucose on AML-12 cells could be partly reversed by a reactive oxygen scavenger (NAC) and caspase-3 specific inhibitor (Z-DEVD-FMK), which suggests high glucose induced GSDME-dependent pyroptosis in AML-12 cells through increasing ROS levels and activating caspase-3. In conclusion, our results show that high glucose can induce pyroptosis in AML-12 cells, at least in part, through the ROS/caspase-3/GSDME pathway,and inhibition of caspase-3 can ameliorate high glucose-induced hepatocyte injury, providing an important basis for clarifying the pathogenesis and treatment of DLI.

5.
QJM ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710498

RESUMEN

BACKGROUND: Temporomandibular disorders (TMD) is the leading cause of pain and disability among frequently occurring facial pain and the second leading cause of musculoskeletal conditions. AIM: We examined whether acupuncture could alleviate pain intensity in patients with temporomandibular disorders (TMD). DESIGN AND METHODS: Sixty participants with TMD were randomly assigned (ratio 1:1) to receive three acupuncture or sham acupuncture sessions weekly for 4 weeks. The primary outcome was the change in the mean weekly pain intensity from baseline to week 4. Secondary and exploratory outcomes included proportion of participants with ≥30% or ≥ 50% reduction in pain intensity, change in jaw opening and movement, graded chronic pain scale, jaw functional limitations scale-20-item, Depression, Anxiety and Stress Scales-21, Pittsburgh sleep quality index at week 4 and 8, and the pressure pain threshold and surface electromyography at week 4. RESULTS AND CONCLUSION: The acupuncture group showed significantly reduced pain intensity compared to the sham group at week 4 (-1.49, 95% confidence interval [CI]: -2.32 to -0.65; P < 0.001) and week 8 (-1.23, 95% CI: -2.11 to -0.54; P = 0.001). Acupuncture's effectiveness surpassed sham's at 4 weeks and lasted 8 weeks. Participants in the acupuncture group experienced significantly greater improvements in the 30% and 50% response rate, jaw opening and movement, GCPS, JFLS-20, DASS-21 and PSQI than those in the sham acupuncture group. There were no significant between-group differences in PPT and sEMG. In summary, acupuncture provided marked pain relief and improvement in physical and emotional function for patients with TMD compared with sham acupuncture.

6.
Plant Dis ; 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38764341

RESUMEN

In Henan, strawberry cultivation occurs on approximately 10,000 hectares, with annual production approaching 230,000 tons. In April 2022, a root rot disease with a 10% incidence rate was observed on the strawberry cultivars 'Ningyu' and 'Sweet Charlie' grown in plastic greenhouses (0.7 ha) located in Xingyang (113.39°E, 34.79°N), Henan, China. Disease symptoms included yellowing of the outer mature leaves, stunted growth, and subsequent wilting of the entire plant. The roots developed dark brown spots, which gradually turned necrotic (Figures 1a, 1b). To determine the causal agent, four symptomatic plants (two plants per cultivar) were collected. Twelve symptomatic root tissues (three root tissue samples per plant) were surface sterilized with 75% ethanol and 0.1% mercuric chloride, washed thrice in sterile water, air dried, and then placed on PDA at 25°C for 3 days. Eight pure isolates were obtained by hyphal-tip isolation (Fang 2007). Each colony had a dark olivaceous green to brown, cottony appearance with a round margin, and the reverse side was grey-black near the center (Figure 1c). Conidia were ellipsoidal, aseptate, with rounded ends, and 3.1 to 4.8 µm × 1.0 to 2.5 µm in size (Figure 1d). Chlamydospores were ellipsoidal, pale brown, and 7.9 to 11.9 µm × 7.6 to 10.7 µm in size (Figure 1e). A representative fungus isolate, designated as Z5, was selected for further molecular identification. Genomic DNA was extracted from the mycelia of isolate Z5, and four gene partial regions (ITS, TUB2, RPB2, and LSU) were amplified using the primer pairs ITS1/ITS4, Bt-2a/Bt-2b, RPB2-5F/RPB2-7CR and LROR/LR5, respectively (White et al.1990, O'Donnell et al.1997, Reeb et al. 2004, Rehner and Samuels 1994). PCR products were sequenced and submitted to GenBank with the following accession numbers OQ130480 (ITS), OQ190093 (TUB2), OQ190092 (RPB2), and OQ255570 (LSU). BLASTn search revealed that the ITS, TUB2, RPB2, and LSU gene sequences of isolate Z5 showed 99.42% (513/516 bp), 99.69% (320/321 bp), 100% (1071/1071 bp), and 100% (857/857 bp) identity with those of ex-type S. pogostemonis stain ZHKUCC 21-0001 (Dong et al. 2021), respectively. A phylogenetic tree was constructed showing that Z5 clustered with S. pogostemonis (Figure 2). The isolates in this study were identified as S. pogostemonis based on morphological and molecular evidence. To confirm pathogenicity, five one-month-old 'Ningyu' cultivar strawberry seedlings were planted in sterilized nursery soil mixed with wheat grains (0.5% w/w) coated with Z5 mycelia (Fang 2007). An equal number of strawberry seedlings were placed in pots filled with non-infected potting mix to serve as controls. The seedlings were kept in a greenhouse under a 12 h light/dark photoperiod at 25°C. After two weeks, the inoculated seedlings displayed symptoms such as leaf wilting and root necrosis, similar to those observed in the greenhouses, while the control seedlings showed no symptoms (Figures 1f, 1g). The experiment was performed thrice. The identical fungus was re-isolated from the symptomatic roots and identified as S. pogostemonis based on morphological characteristics and molecular analysis, thus fulfilling Koch's postulates. This is the first report of S. pogostemonis causing root rot on strawberries worldwide. Our findings will contribute to a more comprehensive study on investigating and managing this disease.

7.
J Vasc Surg Venous Lymphat Disord ; : 101905, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38761979

RESUMEN

OBJECTIVE: Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, Supraclavicular vascularized lymph node transfer (SC-VLNT) is a favoured approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction. METHODS: A cohort of 35 patients with GC-LEL was examined, comprising thirteen patients underwent single lymph nodes flap with a skin paddle (SLNF+P), twelve received single lymph nodes flap without a skin paddle (SLNF), and ten accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and post-operative variables. RESULTS: The median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patient noted subjective improvements in Lymphedema Quality of Life (LYMQOL) scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage Ⅱ). The median follow-up time was 16 months (range, 12 to 36 months), with no reported severe postoperative complications. CONCLUSION: For advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization.

8.
Proc Natl Acad Sci U S A ; 121(21): e2321958121, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38748584

RESUMEN

Understanding the stability mechanism of surface micro/nanobubbles adhered to gas-evolving electrodes is essential for improving the efficiency of water electrolysis, which is known to be hindered by the bubble coverage on electrodes. Using molecular simulations, the diffusion-controlled evolution of single electrolytic nanobubbles on wettability-patterned nanoelectrodes is investigated. These nanoelectrodes feature hydrophobic islands as preferential nucleation sites and allow the growth of nanobubbles in the pinning mode. In these simulations, a threshold current density distinguishing stable nanobubbles from unstable nanobubbles is found. When the current density remains below the threshold value, nucleated nanobubbles grow to their equilibrium states, maintaining their nanoscopic size. However, for the current density above the threshold value, nanobubbles undergo unlimited growth and can eventually detach due to buoyancy. Increasing the pinning length of nanobubbles increases the degree of nanobubble instability. By connecting the current density with the local gas oversaturation, an extension of the stability theory for surface nanobubbles [Lohse and Zhang, Phys. Rev. E 91, 031003(R) (2015)] accurately predicts the nanobubble behavior found in molecular simulations, including equilibrium contact angles and the threshold current density. For larger systems that are not accessible to molecular simulations, continuum numerical simulations with the finite difference method combined with the immersed boundary method are performed, again demonstrating good agreement between numerics and theories.

9.
Burns Trauma ; 12: tkad060, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585341

RESUMEN

Acne is a common chronic inflammatory dermatosis that can lead to pathological scars (PSs, divided into hypertrophic scars and keloids). These kinds of abnormal scars seriously reduce the quality of life of patients. However, their mechanism is still unclear, resulting in difficult clinical prevention, unstable treatment effects and a high risk of recurrence. Available evidence supports inflammatory changes caused by infection as one of the keys to abnormal proliferation of skin fibroblasts. In acne-induced PSs, increasing knowledge of the immunopathology indicates that inflammatory cells directly secrete growth factors to activate fibroblasts and release pro-inflammatory factors to promote the formation of PSs. T helper cells contribute to PSs via the secretion of interleukin (IL)-4 and IL-13, the pro-inflammatory factors; while regulatory T cells have anti-inflammatory effects, secrete IL-10 and prostaglandin E2, and suppress fibrosis production. Several treatments are available, but there is a lack of combination regimens to target different aspects of acne-induced PSs. Overall, this review indicates that the joint involvement of inflammatory response and fibrosis plays a crucial role in acne-induced PSs, and also analyzes the interaction of current treatments for acne and PS.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38598173

RESUMEN

Motivated by the surging demand for low-temperature waste heat harvesting, materials with both prominent thermoelectric and good mechanical properties are preferred in practical applications. In this present work, the composite exploration of Te-doped Mg3.2Bi1.5Sb0.5-x vol % nanosized SiC (x = 0, 0.05, 0.1, 0.2, and 0.5) was carried out, where nanosized SiC is physically dispersed in the matrix in the form of a second phase. SiC second phase compositing further optimized the matrix carrier concentration, resulting in a higher power factor in the service temperature range (the highest value from 28.9 to 31.7 µW cm-1 K-2), and the (ZT)ave from 0.91 to 0.96 compared with the matrix sample. In addition, the SiC second phase effectively enhanced the mechanical properties of composite materials, including flexural strength, microhardness, and modulus. Because of the simultaneous optimization of thermoelectric and mechanical properties, the overall performance of Te-doped Mg3.2Bi1.5Sb0.5-0.05 vol % SiC composite is leveraged to meet special requirements of power generation. It is expected that the addition of SiC should be broadly applicable to address the physical performance in other thermoelectric systems.

11.
Planta ; 259(5): 119, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594473

RESUMEN

MAIN CONCLUSION: S. plumbizincicola genetic transformation was optimized using a self-excision molecular-assisted transformation system by integrating the SpGRF4/SpGIF1 gene with XVE and Cre/loxP. Sedum plumbizincicola, despite being an excellent hyperaccumulator of cadmium and zinc with significant potential for soil pollution phytoremediation on farmland, has nonetheless trailed behind other major model plants in genetic transformation technology. In this study, different explants and SpGRF4-SpGIF1 genes were used to optimize the genetic transformation of S. plumbizincicola. We found that petiole and stem segments had higher genetic transformation efficiency than cluster buds. Overexpression of SpGRF4-SpGIF1 could significantly improve the genetic transformation efficiency and shorten the period of obtaining regenerated buds. However, molecular assistance with overexpression of SpGRF4-SpGIF1 leads to abnormal morphology, resulting in plant tissue enlargement and abnormal growth. Therefore, we combined SpGRF4-SpGIF1 with XVE and Cre/loxP to obtain DNA autocleavage transgenic plants induced by estradiol, thereby ensuring normal growth in transgenic plants. This study optimized the S. plumbizincicola genetic transformation system, improved the efficiency of genetic transformation, and established a self-excision molecular-assisted transformation system. This work also established the basis for studying S. plumbizincicola gene function, and for S. plumbizincicola breeding and germplasm innovation.


Asunto(s)
Sedum , Contaminantes del Suelo , Fitomejoramiento , Cadmio , Biodegradación Ambiental , Transformación Genética , Suelo
12.
ACS Omega ; 9(16): 18032-18045, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38680313

RESUMEN

Spherical δ-MnO2 nanoflower materials were synthesized via a facile one-step coprecipitation method through adjusting the molar ratio of KMnO4 to MnSO4. The influence of the molar ratio of the reactants on the crystal structure, morphology, and electrochemical performances was investigated. At a molar ratio of 3.3 for KMnO4 to MnSO4, the spherical δ-MnO2 nanoflowers composed of nanosheets with the highest specific surface area (228.0 m2 g-1) were obtained as electrode materials. In the conventional three-electrode system using 1 M Na2SO4 as an electrolyte, the specific capacitance of the spherical δ-MnO2 nanoflowers reached 172.3 F g-1 at a current density of 1 A g-1. Moreover, even after 5000 cycles at a current density of 5 A g-1, the GCD curves remained essentially unchanged, and the specific capacitance still retained 86.50% of the maximum value. The kinetics of the electrode reaction were preliminarily studied through the linear potential sweep technique to observe diffusion-controlled contribution toward total capacitance. For the spherical δ-MnO2 nanoflower electrode material, diffusion-controlled contribution accounted for 65.1% at low scan rates and still remained significant at high scan rates (100 mV s-1), indicating excellent utilization efficiency of the bulk phase. The as-fabricated asymmetric supercapacitor HFC-7//MnO2-3.3-ASC presented a prominent specific energy of 16.5 Wh kg-1 at the specific power of 450 W kg-1. Even when the specific power reached 9.0 kW kg-1, the energy density still retained 9.5 Wh kg-1.

13.
J Pharm Anal ; 14(4): 100899, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38634061

RESUMEN

Tyrosine kinase inhibitors (TKIs) have emerged as the first-line small molecule drugs in many cancer therapies, exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways. However, there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites, which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments, alongside other potential side effects or adverse reactions. Therefore, an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods, clinical pharmacokinetics, and therapeutic drug monitoring of different TKIs. This paper provides a comprehensive overview of the advancements in pretreatment methods, such as protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE), micro-SPE (µ-SPE), magnetic SPE (MSPE), and vortex-assisted dispersive SPE (VA-DSPE) achieved since 2017. It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) methods, capillary electrophoresis (CE), gas chromatography (GC), supercritical fluid chromatography (SFC) procedures, surface plasmon resonance (SPR) assays as well as novel nanoprobes-based biosensing techniques. In addition, a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

14.
Neurology ; 102(9): e209305, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38630960

RESUMEN

BACKGROUND AND OBJECTIVES: Structural imaging can offer insights into the cortical morphometry of migraine, which might reflect adaptations to recurring nociceptive messaging. This study compares cortical morphometry between a large sample of people with migraine and healthy controls, as well as across migraine subtypes. METHODS: Adult participants with migraine and age-matched and sex-matched healthy controls attended a single MRI session with magnetization-prepared rapid acquisition gradient echo and fluid-attenuated inversion recovery sequences at 3T. Cortical surface area, thickness, and volume were compared between participants with migraine (including subgroups) and healthy controls across the whole cortex within FreeSurfer and reported according to the Desikan-Killiany atlas. The analysis used cluster-determining thresholds of p < 0.0001 and cluster-wise thresholds of p < 0.05, adjusted for age, sex, and total intracranial volume. RESULTS: A total of 296 participants with migraine (mean age 41.6 years ± 12.4 SD, 261 women) and 155 healthy controls (mean age 41.1 years ± 11.7 SD, 133 women) were included. Among the participants with migraine, 180 (63.5%) had chronic migraine, 103 (34.8%) had migraine with aura, and 88 (29.7%) experienced a migraine headache during the scan. The total cohort of participants with migraine had reduced cortical surface area in the left insula, compared with controls (p < 0.0001). Furthermore, participants with chronic migraine (n = 180) exhibited reduced surface area in the left insula (p < 0.0001) and increased surface area in the right caudal anterior cingulate cortex (p < 0.0001), compared with controls. We found no differences specific to participants with aura or ongoing migraine headache. Post hoc tests revealed a positive correlation between monthly headache days and surface area within the identified anterior cingulate cluster (p = 0.014). DISCUSSION: The identified cortical changes in migraine were limited to specific pain processing regions, including the insula and caudal anterior cingulate gyrus, and were most notable in participants with chronic migraine. These findings suggest persistent cortical changes associated with migraine. TRIAL REGISTRATION INFORMATION: The REFORM study (clinicaltrials.gov identifier: NCT04674020).


Asunto(s)
Trastornos Migrañosos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Giro del Cíngulo , Cefalea , Imagen por Resonancia Magnética/métodos , Sistema de Registros
15.
CNS Neurosci Ther ; 30(4): e14711, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38644551

RESUMEN

OBJECTIVE: To elucidate the relationship between USP19 and O(6)-methylguanine-DNA methyltransferase (MGMT) after temozolomide treatment in glioblastoma (GBM) patients with chemotherapy resistance. METHODS: Screening the deubiquitinase pannel and identifying the deubiquitinase directly interacts with and deubiquitination MGMT. Deubiquitination assay to confirm USP19 deubiquitinates MGMT. The colony formation and tumor growth study in xenograft assess USP19 affects the GBM sensitive to TMZ was performed by T98G, LN18, U251, and U87 cell lines. Immunohistochemistry staining and survival analysis were performed to explore how USP19 is correlated to MGMT in GBM clinical management. RESULTS: USP19 removes the ubiquitination of MGMT to facilitate the DNA methylation damage repair. Depletion of USP19 results in the glioblastoma cell sensitivity to temozolomide, which can be rescued by overexpressing MGMT. USP19 is overexpressed in glioblastoma patient samples, which positively correlates with the level of MGMT protein and poor prognosis in these patients. CONCLUSION: The regulation of MGMT ubiquitination by USP19 plays a critical role in DNA methylation damage repair and GBM patients' temozolomide chemotherapy response.


Asunto(s)
Antineoplásicos Alquilantes , Metilación de ADN , Metilasas de Modificación del ADN , Enzimas Reparadoras del ADN , Resistencia a Antineoplásicos , Temozolomida , Proteínas Supresoras de Tumor , Humanos , Temozolomida/farmacología , Temozolomida/uso terapéutico , Enzimas Reparadoras del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Metilasas de Modificación del ADN/metabolismo , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Animales , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Metilación de ADN/efectos de los fármacos , Ratones Desnudos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Ratones , Masculino , Femenino , Dacarbazina/análogos & derivados , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Reparación del ADN/efectos de los fármacos , Endopeptidasas/metabolismo , Endopeptidasas/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Ubiquitinación/efectos de los fármacos
16.
Org Biomol Chem ; 22(17): 3381-3385, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38606462

RESUMEN

A method for generation of SVI sulfones from ß-sulfinyl esters (SIV) under transition-metal-free non-oxidative mild conditions is presented. Various sulfones have been achieved with moderate to excellent yields. The advantage of using ß-sulfinyl esters as masked aryl sulfinates has also been exemplified using brominated substrates. Oxygen isotope-labeling experiments indicated that the oxygen atoms incorporated into the sulfone product come from the sulfoxide of the ß-sulfinyl ester. Successive ß-elimination/O-addition/sulfinate esterification/ß-elimination processes are proposed for the mechanism of generating SVI from SIV.

17.
Bioact Mater ; 36: 48-61, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38434148

RESUMEN

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.

18.
Environ Res ; 251(Pt 1): 118643, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38458590

RESUMEN

Coal gasification fine slag (CGFS), as a difficult-to-dispose solid waste in the coal chemical industry, consists of minerals and residual carbon. Due to the aggregate structure of minerals blocking pores and encapsulating active substances, the high-value utilization of CGFS still remains a challenge. Based on the intrinsic characteristics of CGFS, this study synthesized Fe-N doped porous carbon/silicate composites (Fe-NC) by alkali activation and pyrolysis for electrocatalytic degradation of phenolic wastewater. Meanwhile, minerals were utilized to regulate the surface chemical and pore structure, turning their disadvantages into advantages, which caused a sharp increase in m-cresol mineralization. The positive effect of minerals on composite properties was investigated by characterization techniques, electrochemical analyses and density functional theory (DFT) calculations. It was found that the mesoporous structure of the mineral-regulated composites was further developed, with more carbon defects and reactive substances on its surface. Most importantly, silicate mediated iron conversion through strong interaction with H2O2, high work function gradient with electroactive iron, and excellent superoxide radical (•O2-) production capacity. It effectively improved the reversibility and kinetics of the entire electrocatalytic reaction. Within the Fe-NC311 electrocatalytic system, the m-cresol removal rate reached 99.55 ± 1.24%, surpassing most reported Fe-N-doped electrocatalysts. In addition, the adsorption and electrooxidation experiment confirmed that the synergistic effect of Fe-N doped porous carbon and silicate simultaneously promoted the capture of pollutants and the transformation of electroactive molecules, and hence effectively shortened the diffusion path of short-lived radicals, which was further supported by molecular dynamics simulation. Therefore, this research provides new insights into the problem of mineral limitations and opens an innovative approach for CGFS recycling and environmental remediation.

19.
Proteomics Clin Appl ; : e2300032, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456388

RESUMEN

PURPOSE: Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR. EXPERIMENTAL DESIGN: Serum disease-specific haptoglobin-ß (Hp-ß) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry. RESULTS: Fucosylation of Hp-ß was significantly increased and sialylation of Hp-ß was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p < 0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-ß was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR. CONCLUSION: Changes in Hp-ß glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.

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