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1.
J Colloid Interface Sci ; 677(Pt A): 208-216, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39089127

RESUMO

The acceleration of active sites formation through surface reconstruction is widely acknowledged as the crucial factor in developing high-performance oxygen evolution reaction (OER) catalysts for water splitting. Herein, a simple one-step corrosion method and magnesium (Mg)-promoted strategy are reported to develop the NiFe-based catalyst with enhanced OER performance. The Mg is introduced in NiFe materials to preparate a "pre-catalyst" Mg-Ni/Fe2O3. In-situ Raman shows that Mg doping would accelerate the self-reconstruction of Ni/Fe2O3 to form active NiOOH species during OER. In-situ infrared indicates that Mg doping benefits the formation of *OOH intermediate. Theoretical analysis further confirms that Mg doping can optimize the adsorption of oxygen intermediates, accelerating the OER kinetics. Accordingly, the Mg-Ni/Fe2O3 catalyst exhibits excellent OER performance with overpotential of 168 mV at 10 mA cm-2. The anion exchange membrane water electrolyzer achieved 200 mA cm-2 at voltage of 1.53 V, showing excellent stability over 500 h as well. This work demonstrates the potential of Mg-promoted strategy in regulating the activity of transition metal-based OER electrocatalysts.

2.
Front Endocrinol (Lausanne) ; 15: 1425426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39355613

RESUMO

Rationale: MG53's known function in facilitating tissue repair and anti-inflammation has broad applications to regenerative medicine. There is controversy regarding MG53's role in the development of type 2 diabetes mellitus. Objective: This study aims to address this controversy - whether MG53's myokine function contributes to inhibition of insulin signaling in muscle, heart, and liver tissues. Study design: We determined the binding affinity of the recombinant human MG53 (rhMG53) to the insulin receptor extracellular domain (IR-ECD) and found low affinity of interaction with Kd (>480 nM). Using cultured C2C12 myotubes and HepG2 cells, we found no effect of rhMG53 on insulin-stimulated Akt phosphorylation (p-Akt). We performed in vivo assay with C57BL/6J mice subjected to insulin stimulation (1 U/kg, intraperitoneal injection) and observed no effect of rhMG53 on insulin-stimulated p-Akt in muscle, heart and liver tissues. Conclusion: Overall, our data suggest that rhMG53 can bind to the IR-ECD, however has a low likelihood of a physiologic role, as the Kd for binding is ~10,000 higher than the physiologic level of MG53 present in the serum of rodents and humans (~10 pM). Our findings question the notion proposed by Xiao and colleagues - whether targeting circulating MG53 opens a new therapeutic avenue for type 2 diabetes mellitus and its complications.


Assuntos
Insulina , Fígado , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt , Receptor de Insulina , Animais , Humanos , Camundongos , Fosforilação/efeitos dos fármacos , Receptor de Insulina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Insulina/metabolismo , Insulina/farmacologia , Miocárdio/metabolismo , Células Hep G2 , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Masculino , Transdução de Sinais/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Citocinas/metabolismo , Proteínas de Membrana
3.
J Plant Physiol ; 303: 154355, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39357114

RESUMO

In serpentine soils, the low level of calcium relative to magnesium (Ca:Mg) is detrimental to the growth of most plant species. Ecotypic variation in Erythranthe guttata allows for some populations to maintain high photosynthetic rates and biomass despite low Ca:Mg. In this study, the mechanism of tolerance was investigated by treating hydroponically grown plants with either high (1.0) or low (0.02) Ca:Mg growth solutions and assaying excised leaf discs for rates of photosynthesis and disc expansion, and for starch, Ca2+ and Mg2+ ion concentrations. Low Ca:Mg in the assay solutions reduced both photosynthesis and leaf disc expansion after one week of treatment. However, serpentine tissues show stable photosynthetic rates after one week and a recovery in leaf tissue expansion after two weeks exposure to low Ca:Mg conditions. Values for non-serpentine tissues continued to decline. Increased growth of low Ca:Mg treated discs supplied with exogenous sucrose suggests that growth in serpentine-exposed tissues is limited by availability of carbon products from photosynthesis. Serpentine leaves had higher vacuole Mg concentrations than non-serpentine leaves after three weeks of treatment with low Ca:Mg. The combination of elevated starch concentrations, reduced growth and lower vacuolar Mg concentrations in leaves of non-serpentine plants grown in low Ca:Mg indicate an inefficient use of carbon resources and starch degradation as an observed response to Mg toxicity. Together, these results suggest that serpentine E. guttata exhibits an inducible tolerance to low Ca:Mg through gradual compartmentalization of magnesium to maintain the production and metabolism of photosynthates necessary for growth.

4.
Adv Mater ; : e2410205, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361260

RESUMO

Bioelectronic patches hold promise for patient-comfort wound healing providing simplified clinical operation. Currently, they face paramount challenges in establishing long-term effective electronic interfaces with targeted cells and tissues due to the inconsistent energy output and high bio interface impedance. Here a new electrochemical stimulation technology is reported, using a simple wound patch, which integrates the efficient generation and delivery of stimulation. This is realized by employing a hydrogel bioelectronic interface as an active component in an integrated power source (i.e., Mg battery). The Mg battery enhances fibroblast functions (proliferation, migration, and growth factor secretion) and regulates macrophage phenotype (promoting regenerative polarization and down-regulating pro-inflammatory cytokines), by providing an electric field and the ability to control the cellular microenvironment through chemical release. This bioelectronic patch shows an effective and accelerated wound closure by guiding epithelial migration, mediating immune response, and promoting vasculogenesis. This new electrochemical-mediated therapy may provide a new avenue for user-friendly wound management as well as a platform for fundamental insights into cell stimulation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39367821

RESUMO

Magnesium-ion batteries (MIBs) are a "beyond Li-ion" technology that are hampered by Mg metal reactivity, which motivates the development of anode materials such as tin (Sn) with high theoretical capacity (903 mAh g-1). However, pure Sn is inactive for Mg2+ storage. Herein, Mg alloying with Sn is enabled within dual-phase Bi-Sn anodes, where the optimal composition (Bi66.5Sn33.5) outperformed single-phase Bi and Sn electrodes to deliver high specific capacity (462 mAh g-1 at 100 mA g-1), good cycle life (84% after 200 cycles), and significantly improved rate capability (403 mAh g-1 at 1000 mA g-1). Density functional theory (DFT) calculations revealed that Mg alloys first with Bi and the subsequent formation of the Mg3Bi2//Sn interfaces is energetically more favorable compared to the individual Mg3Bi2 and Sn phases. Mg insertion into Sn is facilitated when Mg3Bi2 is present. Moreover, dealloying Mg from Mg3Bi2:Mg2Sn systems requires the creation of Mg vacancies and subsequent Mg diffusion. Mg vacancy creation is easier for Mg2Sn compared to Mg3Bi2, while the latter has slightly lower activated Mg-diffusion pathways. The computational findings point toward easier magnesiation/demagnesiation for BiSn alloys over pure Bi or pure Sn, corroborating the superior Mg storage performance of Bi-Sn electrodes over the corresponding single-phase electrodes.

6.
Food Chem ; 463(Pt 4): 141497, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39368201

RESUMO

Herein, an electrochemical aptasensor for highly sensitive detection of acetamiprid (ACE) was constructed based on a one-step cascade amplification strategy. This innovative strategy integrated DNA walker containing DNAzyme sequence into entropy-driven catalysis (EDC) system. The trigger strand was released by aptamer-specific binding to ACE, initiating the EDC amplification circuit and delivering DNA walker strands. The dangling DNA walker continuously bound and cleaved hairpin substrate to form G-quadruplex fragments with the assistance of Mg2+. The G-quadruplex fragments folded and captured hemin to form multitudinous G-quadruplex/hemin complexes in the presence of K+, generating significantly enhanced current, enabling enzyme-free, label-free and highly sensitive detection of ACE, with a linear detection range of 100 fM to 50 nM and a detection limit of 68.36 fM (S/N = 3). The constructed aptasensor achieved the reliable detection of ACE in vegetable soil and cucumber samples, demonstrating its potential application prospects in environmental protection and food supervision.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39354755

RESUMO

BACKGROUND: Tumor cell resistance to cisplatin is a common challenge in endometrial cancer chemotherapy, stemming from various mechanisms. Targeted therapies using proteasome inhibitors, such as MG132, have been investigated to enhance cisplatin sensitivity, potentially offering a novel treatment approach. OBJECTIVE: The aim of this study was to investigate the effects of MG132 on cisplatin sensitivity in the human endometrial cancer (EC) cell line RL95-2, focusing on cell proliferation, apoptosis, and cell signaling. METHODS: Human endometrial cancer RL95-2 cells were exposed to MG132, and cell viability was assessed in a dose-dependent manner. The study evaluated the effect of MG132 on cisplatin-induced proliferation inhibition and apoptosis, correlating with caspase-3 activation and reactive oxygen species (ROS) upregulation. Additionally, we examined the inhibition of the ubiquitin-proteasome system and the expression of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, and IL-13 during MG132 and cisplatin co-administration. RESULTS: MG132 exposure significantly reduced cell viability in a dose-dependent manner. It augmented cisplatin- induced proliferation inhibition and enhanced apoptosis, correlating with caspase-3 activation and ROS upregulation. Molecular analysis revealed a profound inhibition of the ubiquitin-proteasome system. MG132 also significantly increased the expression of cisplatin-induced pro-inflammatory cytokines, suggesting a transition from chronic to acute inflammation. CONCLUSION: MG132 enhances the therapeutic efficacy of cisplatin in human EC cells by suppressing the ubiquitin- proteasome pathway, reducing cell viability, enhancing apoptosis, and shifting the inflammatory response. These findings highlighted the potential of MG132 as an adjuvant in endometrial cancer chemotherapy. Further research is needed to explore detailed mechanisms and clinical applications of this combination therapy.

8.
Adv Sci (Weinh) ; : e2409788, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352315

RESUMO

With the advances in bulk Mg3Bi2, there is increasing interest in pursuing whether Mg3Bi2 can be fabricated into flexible thin films for wearable electronics to expand the practical applications. However, the development of fabrication processes for flexible Mg3Bi2 thin films and the effective enhancement of their thermoelectric performance remain underexplored. Here, magnetron sputtering and ex-situ annealing techniques is used to fabricate flexible Mg3Bi2 thermoelectric thin films with a power factor of up to 1.59 µW cm-1 K-2 at 60 °C, ranking as the top value among all reported n-type Mg3Bi2 thin films. Extensive characterizations show that ex-situ annealing, and optimized sputtering processes allow precise control over film thickness. These techniques ensure high adhesion of the films to various substrates, resulting in excellent flexibility, with <10% performance degradation after 500 bending cycles with a radius of 5 mm. Furthermore, for the first time, flexible thermoelectric devices are fabricated with both p-type and n-type Mg3Bi2 legs, which achieve an output power of 0.17 nW and a power density of 1.67 µW cm-2 at a very low temperature difference of 2.5 °C, highlighting the practical application potential of the device.

9.
Regen Biomater ; 11: rbae104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372848

RESUMO

Facilitating an appropriate immune response is crucial for promoting bone tissue regeneration upon biomaterial implantation. In this study, the Mg2+-containing nanostructures on the surface of Ti-1.25Mg alloy were prepared by a one-step hydrothermal reaction method via regulating pH value to enhance the immunomodulatory osteogenic properties of Ti-Mg alloys. In neutral (HT7) or alkaline (HT9) hydrothermal treatment (HT) solution, the size of MgTiO3 nanostructures formed on the surface of Ti-1.25Mg alloy is smaller than that in acidic HT solution (HT5), and lamellar Mg(OH)2 nanostructures are found in HT7 and HT9. In addition, the sample surface has a lower roughness and higher wettability with increasing pH value. The Mg2+-containing nanostructures on the Ti-1.25Mg alloy inhibited inflammatory response by promoting the polarization of M2 macrophages, thereby promoting osteogenesis in vitro. The micro-CT and histological assessment proved that the regeneration of bone defect was faster in HT7 than the Ti-1.25Mg in vivo. Mechanically, Mg2+-containing nanostructures can mediate the immune response of macrophages via upregulating integrins α5ß1 and inhibiting Toll-like receptors (TLR-4), subsequently inhibiting the NF-κB signaling pathway. Overall, osteoimmunity-regulating Mg2+-containing nanostructures on Ti-1.25Mg present a promising biomaterial for bone repair.

10.
J Environ Manage ; 370: 122729, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39369533

RESUMO

Elevated levels of total hardness in drinking water can readily result in scaling, which poses a threat to both the safety of water quality and the convenience of its use. While there is a wealth of research on the removal of calcium hardness, there is a dearth of studies focusing on the removal of magnesium hardness. In light of this, the present study employs modified induced crystallization softening (MICS) to delineate the removal pathways and mechanisms of magnesium hardness, and to investigate viable methods for its enhancement and application. Our research has determined that magnesium hardness can be effectively removed from water through the MICS, with the dosage of softening agents (NaOH) being a significant factor that influences this removal, whereas the fixed bed height within the fluidized bed exerts minimal impact on the process. In the low-dose stage (less than 250 mg/L), when the pH is below 10.0, up to 20% of magnesium hardness can be removed, predominantly through the crystallization of (Ca0.936Mg0.064)CO3. As the dosage increases to the moderate stage (250-400 mg/L), the conversion of excess bicarbonate (HCO3-) to carbonate (CO32-) in the water hinders further removal of magnesium hardness. In the high-dose stage (exceeding 400 mg/L), when the pH rises above 10.5, the removal rate of magnesium hardness can be enhanced to over 75%, with the crystallization of Mg(OH)2 being the primary removal mechanism. Density functional theory calculations, along with molecular dynamics simulations of cohesive energy and bond energy, substantiate the feasibility of the identified magnesium removal pathways. The addition of coagulants (FeCl3) and an decrease in the up-flow velocity can further augment the removal efficiency of magnesium hardness by promoting the crystallinity of Mg(OH)2 during the high-dose stage (exceeding 400 mg/L). In practical engineering applications, the strategic control of softening agent dosages enables the achievement of varying levels of magnesium hardness removal, tailored to specific water quality requirements.

11.
Artigo em Inglês | MEDLINE | ID: mdl-39373289

RESUMO

The demand for high-performance microwave dielectric ceramics has surged with the proliferation of fifth-generation (5G) communication networks. In this work, SrLa(Al0.50-xGaxZn0.125Mg0.125Ti0.25)O4 (x = 0-0.20) ceramics were designed by leveraging the unique properties of SrLaAlO4 ceramics and high-entropy engineering. The effects of configurational entropy (Sconf = 1.23R - 1.54R) on the mechanical, thermal, and microwave dielectric properties of SrLa(Al0.50-xGaxZn0.125Mg0.125Ti0.25)O4 ceramics were investigated. X-ray diffractometer and transmission electron microscope analyses confirmed that each composition belonged to the tetragonal structure with a space group of I4/mmm. Significant improvements in Vickers hardness were observed with increasing Sconf, reaching 8.05 GPa at Sconf = 1.54R compared to 5.64 GPa in SrLaAlO4 ceramics. Additionally, the increasing entropy showed great potential in reducing the thermal expansion coefficient (CTE) from 12.32 to 11.49 ppm/°C. The optimal quality factor (Q × f) of 98,000 GHz was achieved at Sconf = 1.37R, attributed to the optimization of intrinsic lattice energy and infrared-damped modes. The temperature coefficient of resonant frequency (τf) was successfully modified toward zero due to entropy-driven CTE and structural modifications. Excellent microwave dielectric properties with εr = 22.5, Q × f = 98,000 GHz, and τf = -2.0 ppm/°C were obtained at Sconf = 1.37R. This work highlights the potential of entropy-engineering in developing high-performance microwave dielectric ceramics, offering a promising pathway for the advancement of 5G communication components.

12.
Cureus ; 16(9): e68664, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39376806

RESUMO

BACKGROUND: Tumor lysis syndrome (TLS) is a critical and potentially fatal complication linked to specific types of cancer. Rasburicase stands as a crucial medication necessary for the prevention and treatment of hyperuricemia, a condition commonly associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed-dose strategy of 3 mg rasburicase was used in many adult cancer patients in our center. OBJECTIVE: The objective of this study was to assess the effectiveness of a fixed dose of 3 mg rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. METHODS:  We conducted a retrospective, observational cohort study between March 2020 and February 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum uric acid (UA) levels at 24 and 48 hours after treatment, with the aim of achieving and maintaining normal UA levels. RESULTS:  Seventeen patients in the treatment group and 20 patients in the prevention group were included. In the treatment group, 15 (88%) patients had normalization of serum UA, which is considered to be <7 mg/dL (median: 4.48 mg/dL) at 24 hours, and 16 (94%) patients had achieved normal UA at 48 hours (median: 2.78 mg/dL) after receiving the rasburicase dose. In the prevention group, all 20 (100%) patients achieved normal UA at 24 hours after receiving the rasburicase dose. CONCLUSION: Based on these findings, a single fixed dose of 3 mg rasburicase is effective for preventing and managing hyperuricemia associated with TLS in high-risk patients.

13.
Cureus ; 16(9): e68895, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39376877

RESUMO

Myasthenia gravis (MG) is an autoimmune disorder affecting postsynaptic membranes in neuromuscular junctions, presenting as fatigable muscle weakness. Myasthenic crisis is a life-threatening complication characterized by severe respiratory insufficiency necessitating invasive or noninvasive ventilation. Two rapid therapies used to manage myasthenic crises are intravenous immunoglobulins (IVIg) and plasmapheresis (PLEX). Their comparative effectiveness remains equivocal. Our article examines evidence from several clinical trials and observational studies, in order to determine the superiority of one treatment over the other. Multiple factors can complicate the choices between two treatments. We concluded that the choice between PLEX and IVIg is multifaceted, guided by individual patient characteristics, institutional resources, and clinician preference. While PLEX can be considered as first-line for rapid clinical outcomes, it is hard to pick one treatment over the other, and careful consideration of comorbidities and resource availability is crucial. Our article highlights the need for further research to establish definitive guidelines and enhance patient outcomes in myasthenic crisis patients.

14.
ACS Nano ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377230

RESUMO

Rechargeable magnesium batteries are attractive candidates for large-scale energy storage applications because of the low cost and high safety, but the scarcity and inferior performance of the cathode materials are hindering the development. In the present study, a kind of copper tetrathiovanadate (Cu3VS4) cathode is designed and developed with a comprehensive consideration of the chemical and electronic structures. The vanadium and sulfur atoms form chemical bonds with high covalent proportion, facilitating electron delocalization via the vanadium-sulfur bonds. This reduces the interaction with the bivalent magnesium cation and induces the coredox of vanadium and sulfur. The crystal structure of Cu3VS4 has interlaced 3D tunnels for solid-state magnesium cation transport. The Cu3VS4 cathode shows a high capacity of 350 mA h g-1 at 100 mA g-1, an outstanding rate performance of 67 mA h g-1 at 10 A g-1, and stable cycling for 1000 cycles at 5 A g-1 without obvious capacity fading. Prominently, a high areal mass load of 3.5 mg cm-2 could be achieved without obvious rate capability decay, which is quite favorable to pair with the high-capacity magnesium metal anode in practical application. The mechanism investigation and theoretical computation demonstrate that Cu3VS4 undergoes first a magnesium intercalation and then a displacement reaction, during which the crystal structure is maintained, assisting the reaction reversibility and cycling stability. All the copper, vanadium, and sulfur elements experience redox and contribute to the high capacity. Moreover, the weakened interaction with magnesium cations, well-kept 3D cation transport tunnels, and high electronic conductivity result in the superior rate performance and high areal active material loading. The present study develops a high-performance cathode for rechargeable magnesium batteries and reveal the design principle based on both of chemical and electronic structures.

15.
Cureus ; 16(9): e68961, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39385918

RESUMO

Juvenile myasthenia gravis is a rare disorder where antibodies targeting the acetylcholine receptor or, less frequently, muscle-specific kinase can be detected in the serum while about half of the patients can be seronegative. A pediatric patient with ocular myasthenia is presented whose serum was negative for acetylcholine receptor and muscle-specific kinase antibodies but tested positive for low-density lipoprotein receptor-related protein 4 antibodies. A favourable clinical response was observed to medical treatment with pyridostigmine and prednisolone, as expected in isolated ocular juvenile myasthenia gravis. This case exemplifies the very rare association of juvenile myasthenia gravis with low-density lipoprotein receptor-related protein 4 positivity, reported in only a few cases so far. The specificity of the antibody and the efficiency of medical treatment emphasize the importance of clinical suspicion and appropriate serological testing in juvenile myasthenia gravis in the absence of acetylcholine receptor and muscle-specific kinase antibodies.

16.
Cureus ; 16(9): e69072, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39391436

RESUMO

Paralabral cysts of the shoulder joint, though rare, often arise from underlying shoulder pathologies such as labral tears and posterior shoulder capsule instability. These mucin-filled cysts can compress surrounding nerves, particularly the suprascapular nerve, leading to muscle weakness, joint instability, and limited range of motion (ROM). Traditionally, management involves magnetic resonance imaging (MRI) diagnosis followed by surgical repair of the underlying pathology and cyst removal. However, less invasive treatments like ultrasound-guided cyst aspiration have shown promising results. In this case, a 48-year-old male with a history of myasthenia gravis (MG) and chronic bilateral shoulder pain presented with worsening right shoulder pain and weakness during exercise. His extensive treatment history included orthopedic surgery on his left shoulder and multiple Platelet-Rich-Plasma (PRP) injections, which offered only temporary relief. After an MRI confirmed a 2.5 cm paralabral cyst compressing the suprascapular nerve, the patient, opting for a non-surgical approach, underwent ultrasound-guided aspiration. The procedure involved a single aspiration session using a 22-gauge needle under real-time ultrasound guidance, with the complete evacuation of cystic fluid. Follow-up at three and six months revealed complete symptom resolution, with a full recovery of muscle strength and shoulder mobility. No complications were observed, and there was no recurrence of the cyst on follow-up imaging. While surgery remains the gold standard, this case underscores the effectiveness of minimally invasive techniques like ultrasound-guided aspiration, which can offer comparable outcomes with potentially lower recurrence rates and reduced morbidity. Studies support image-guided cyst aspiration as a cost-effective, patient-preferred alternative to surgery, with broader implications for clinical practice in managing similar cases. In summary, paralabral cysts present a complex clinical challenge that benefits from individualized treatment plans. In addition, this case highlights the importance of inter-professional communication and patient-centered care in exploring viable alternatives to surgery, such as ultrasound-guided aspiration, which provides significant symptom relief and functional improvement.

17.
J Neuroimmunol ; 396: 578464, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39393213

RESUMO

In our study, we investigated the impact of tacrolimus (TAC) on CD4+ T cell subsets in 41 AChR-MG patients over 12 weeks. Twenty-seven patients were classified as the response group (RG) (improved myasthenia gravis composite scores ≥3), while 14 were non-response. We found that TAC treatment significantly reduced Th17 and pathogenic Th17 cells, along with IL-17 levels in RG, while Th1 and Tfh cells slightly decreased without affecting Th2 or Treg subsets. This indicates that TAC's clinical benefits may be due to its inhibitory effect on the Th17 response, enhancing our insight into its immunomodulatory mechanisms in MG management.

18.
Biochem Biophys Res Commun ; 734: 150638, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39236589

RESUMO

Haploinsufficiency of the nuclear receptor binding SET domain-containing protein 1 gene (NSD1) leads to a neurodevelopmental disorder known as Sotos syndrome (SOTOS). This study investigated the effects of NSD1 knockdown in glial cells. U87MG glioma cells were transfected with siRNA targeting NSD1, which resulted in morphological changes characteristic of activated astrocytes. These activated phenotypes were accompanied by specific activation of mitogen-activated protein kinase (MAPK) signaling pathways, particularly those mediated by p38 MAPK and c-Jun N-terminal kinase (JNK). Transcriptome analysis showed increased expression of proinflammatory cytokine genes, particularly interleukin (IL)-1α, IL-1ß, and IL-6, following NSD1 knockdown. Treatment with MAPK inhibitors significantly reduced the cytokine induction caused by NSD1 knockdown, with the p38 MAPK inhibitor being more effective than the JNK inhibitor. These findings provide new insights into the role of NSD1 loss in neurological dysfunctions associated with SOTOS.

19.
Lipids Health Dis ; 23(1): 282, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232759

RESUMO

OBJECTIVE: This study aimed to reveal the role and mechanism of MG-132 in delaying hyperlipidemia-induced senescence of vascular smooth muscle cells (VSMCs). METHODS: Immunohistochemistry and hematoxylin-eosin staining confirmed the therapeutic effect of MG-132 on arterial senescence in vivo and its possible mechanism. Subsequently, VSMCs were treated with sodium palmitate (PA), an activator (Recilisib) or an inhibitor (Pictilisib) to activate or inhibit PI3K, and CCK-8 and EdU staining, wound healing assays, Transwell cell migration assays, autophagy staining assays, reactive oxygen species assays, senescence-associated ß-galactosidase staining, and Western blotting were performed to determine the molecular mechanism by which MG-132 inhibits VSMC senescence. Validation of the interaction between MG-132 and PI3K using molecular docking. RESULTS: Increased expression of p-PI3K, a key protein of the autophagy regulatory system, and decreased expression of the autophagy-associated proteins Beclin 1 and ULK1 were observed in the aortas of C57BL/6J mice fed a high-fat diet (HFD), and autophagy was inhibited in aortic smooth muscle. MG-132 inhibits atherosclerosis by activating autophagy in VSMCs to counteract PA-induced cell proliferation, migration, oxidative stress, and senescence, thereby inhibiting VSMC senescence in the aorta. This process is achieved through the PI3K/AKT/mTOR signaling pathway. CONCLUSION: MG-132 activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby inhibiting palmitate-induced proliferation, migration, and oxidative stress in vascular smooth muscle cells and suppressing their senescence.


Assuntos
Autofagia , Senescência Celular , Leupeptinas , Músculo Liso Vascular , Miócitos de Músculo Liso , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Autofagia/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Senescência Celular/efeitos dos fármacos , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Leupeptinas/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Ácido Palmítico/farmacologia , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos
20.
Adv Sci (Weinh) ; : e2404150, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269274

RESUMO

Positively charged nanofiltration membranes have attracted much attention in the field of lithium extraction from salt lakes due to their excellent ability to separate mono- and multi-valent cations. However, the thicker selective layer and the lower affinity for Li+ result in lower separation efficiency of the membranes. Here, PEI-P membranes with highly efficient Li+/Mg2+ separation performance are prepared by introducing highly lithophilic 4,7,10-Trioxygen-1,13-tridecanediamine (DCA) on the surface of PEI-TMC membranes using a post-modification method. Characterization and experimental results show that the utilization of the DCA-TMC crosslinked structure as a space-confined layer to inhibit the diffusion of the monomer not only increases the positive charge density of the membrane but also reduces its thickness by ≈35% and presents a unique coffee-ring structure, which ensures excellent water permeability and rejection of Mg2+. The ion-dipole interaction of the ether chains with Li+ facilitates Li+ transport and improves the Li+/Mg2+ selectivity (SLi,Mg = 23.3). In a three-stage nanofiltration process for treating simulated salt lake water, the PEI-P membrane can reduce the Mg2+/Li+ ratio of the salt lake by 400-fold and produce Li2CO3 with a purity of more than 99.5%, demonstrating its potential application in lithium extraction from salt lakes.

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