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1.
Clin Case Rep ; 12(5): e8847, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38770416

RESUMO

Key Clinical Message: Unlike most cases, the lesions were localized to the dorsum of the hand, lacked pruritus (itching), and did not exhibit "sperm-like blood vessels," which are typically pathognomonic to classical MF. Abstract: The study presents a rare case involving a 44-year-old woman who developed a skin condition on the base of her left thumb. Initially misdiagnosed as pigmented purpura, the need for further investigation arose to determine the nature of the condition accurately. The medical evaluation encompassed a comprehensive analysis of the patient's skin ailment. A series of diagnostic examinations were conducted to ascertain the underlying cause. Although routine blood tests yielded unremarkable results, the distinct characteristics of the rash prompted a more thorough investigation. Subsequent assessment revealed that the skin condition was not pigmented purpura, as initially presumed, but rather a manifestation of cutaneous T-cell lymphoma (CTCL) known as mycosis fungoides (MF). MF is an infrequent lymphoma predominantly affecting individuals aged 45-65, exhibiting a male-to-female sex ratio of 2:1. The annual incidence of MF ranges from 0.3 to 0.96 cases per 100,000 individuals. The woman's skin exhibited discrete patches adorned with colored dots, progressively thickening and pigmentation. Notably, the absence of pruritus did not dispel suspicion. This case underscores the significance of accurately diagnosing uncommon dermatological disorders to facilitate appropriate medical intervention. The unique appearance of the rash and its distinctive features, despite normal blood results, enabled the identification of MF. The patient's treatment encompassed a combination of steroids and narrowband UV therapy. Vigilance, continued research, and heightened awareness are paramount for early intervention and improved patient outcomes. Such efforts contribute to an enhanced understanding of the complexities of this condition.

2.
J Bone Miner Res ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753892

RESUMO

Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking from head-to-head randomized trials evaluating fracture outcomes. This retrospective cohort study uses administrative claims data from Medicare fee-for service beneficiaries to evaluate the comparative effectiveness of denosumab versus alendronate in reducing fracture risk among women with postmenopausal osteoporosis (PMO) in the US. Women with PMO ≥ 66 years of age with no prior history of osteoporosis treatment, who initiated denosumab (n = 89 115) or alendronate (n = 389 536) from 2012 to 2018, were followed from treatment initiation until the first of a specific fracture outcome, treatment discontinuation or switch, end of study (December 31, 2019), or other censoring criteria. A doubly robust inverse-probability of treatment and censoring weighted function was used to estimate the risk ratio associated with the use of denosumab compared with alendronate for hip, nonvertebral (NV; includes hip, humerus, pelvis, radius/ulna, other femur), non-hip nonvertebral (NHNV), hospitalized vertebral (HV), and major osteoporotic (MOP; consisting of NV and HV) fractures. Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate. Denosumab reduced the risk of MOP fractures by 9% at year 1, 12% at year 2, 18% at year 3, and 31% at year 5. An increase in the magnitude of fracture risk reduction with increasing duration of exposure was also observed for other NV fracture outcomes. In this cohort of almost half-a-million treatment-naive women with PMO, we observed clinically significant reductions in the risk of MOP, hip, NV, NHNV, and HV fractures for patients on denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk.


Osteoporosis-related fractures can have a significant impact on the health and quality of life of women with postmenopausal osteoporosis (PMO), as well as pose a significant burden to society. Although clinical trials have shown that denosumab is more effective at increasing bone mineral density compared to alendronate, there is a lack of evidence evaluating the fracture risk between these two commonly used osteoporosis therapies. In this study using Medicare claims data for almost 500 000 women with PMO with no prior history of osteoporosis medication use, we compared the risk of fracture, an important outcome to patients and health care providers, between denosumab and alendronate. Advanced analytic methods were implemented to ensure the study results were valid and were not unduly influenced by biases common in observational studies. We observed clinically meaningful reductions (from 30% up to 50%) in the risk of hip, nonvertebral, non-hip nonvertebral, hospitalized vertebral, and major osteoporotic fractures for patients treated with denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk than those who remained on alendronate.

3.
J Exp Bot ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38745476

RESUMO

Trichomes, specialized hair-like structures in the epidermal cells of the aboveground parts of plants, protect plants from pests and pathogens and produce valuable metabolites. Chrysanthemum morifolium, used in tea products, has ornamental and medicinal value. However, it is susceptible to Alternaria alternata fungal infection, posing a threat to its production and use, resulting in substantial economic losses. Increasing the density of glandular trichomes enhances disease resistance and improves the production of medicinal metabolites in chrysanthemums. Jasmonate (JA), promotes the formation of glandular trichomes in various plants. However, it remains unclear whether glandular trichome in chrysanthemums are regulated by JA. Grafting, a technique to improve plant resistance to biotic stresses, has been insufficiently explored in its impact on glandular trichomes, terpenoids, and disease resistance. In this study, we demonstrated that grafting with Artemisia vulgaris rootstocks improves the resistance of chrysanthemum scions to A. alternata. Heterografted chrysanthemums exhibited higher trichome density and terpenoid content compared to self-grafted counterparts. Transcriptome analysis highlighted the significant role of CmJAZ1-like in disease resistance in heterografted chrysanthemums. Overexpressing CmJAZ1-like lines exhibited sensitivity to A. alternate, characterized by reduced glandular trichome density and limited terpenoids. Conversely, silencing lines exhibited resistance to A. alternata showcasing increased glandular trichome density and abundant terpenoids. Higher JA content was confirmed in heterografted chrysanthemum scions compared to self-grafted ones. Furthermore, we established that JA promotes the development of glandular trichomes and the synthesis of terpenoids while inducing the degradation of CmJAZ1-like proteins in chrysanthemums. These findings suggest that higher JA increases trichome density and terpenoid content, enhancing resistance to A. alternata by regulating CmJAZ1-like in heterografted chrysanthemums.

4.
Int J Oral Sci ; 16(1): 40, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740746

RESUMO

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease (AD), particularly in the early stages of the disease. The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases. We herein demonstrated that human dental pulp stem cells (hDPSCs) mediated oxidative stress improvement and neuroreparative effects in in vitro AD models, playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons. Importantly, these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs, with the treated mice showing significant improvement in cognitive function and neuropathological features. Mechanistically, antioxidant and neuroprotective effects, as well as cognitive enhancements elicited by hDPSCs, were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3ß-Nrf2 signaling pathway. In conclusion, our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models, which may be a tremendous potential therapeutic candidate for Alzheimer's disease.


Assuntos
Doença de Alzheimer , Polpa Dentária , Glicogênio Sintase Quinase 3 beta , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Polpa Dentária/citologia , Doença de Alzheimer/terapia , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Modelos Animais de Doenças , Transplante de Células-Tronco , Células-Tronco , Camundongos Transgênicos
5.
IEEE Trans Cybern ; PP2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713573

RESUMO

Efficient monitoring of production performance is crucial for ensuring safe operations and enhancing the economic benefits of the Iron and Steel Corporation. Although basic modeling algorithms and visualization diagrams are available in many scientific platforms and industrial applications, there is still a lack of customized research in production performance monitoring. Therefore, this article proposes an interactive visual analytics approach for monitoring the heavy-plate production process (iHPPPVis). Specifically, a multicategory aggregated monitoring framework is proposed to facilitate production performance monitoring under varying working conditions. In addition, A set of visualizations and interactions are designed to enhance analysts' analysis, identification, and perception of the abnormal production performance in heavy-plate production data. Ultimately, the efficacy and practicality of iHPPPVis are demonstrated through multiple evaluations.

7.
Environ Res ; : 119206, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38782346

RESUMO

Climate warming is a pressing global issue with substantial impacts on soil health and function. However, the influence of environmental context on the responses of soil microorganisms to warming remains largely elusive, particularly in alpine ecosystems. This study examined the responses of the soil microbiome to in situ experimental warming across three elevations (3,850 m, 4,100 m, and 4,250 m) in the meadow of Gongga Mountain, eastern Tibetan Plateau. Our findings demonstrate that soil microbial diversity is highly resilient to warming, with significant impacts observed only at specific elevations. Furthermore, the influence of warming on the composition of the soil microbial community is also elevation-dependent, underscoring the importance of local environmental context in shaping microbial evolution in alpine soils under climate warming. Notably, we identified soil moisture at 3,850 m and carbon-to-nitrogen ratio at 4,250 m as indirect predictors regulating the responses of microbial diversity to warming at specific elevations. These findings underscore the paramount importance of considering pre-existing environmental conditions in predicting the response of alpine soil microbiomes to climate warming. Our study provides novel insights into the intricate interactions between climate warming, soil microbiome, and environmental context in alpine ecosystems, illuminating the complex mechanisms governing soil microbial ecology in these fragile and sensitive environments.

8.
J Med Chem ; 67(10): 7836-7858, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38695063

RESUMO

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment.


Assuntos
Antineoplásicos , Mutação , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Humanos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Camundongos , Linhagem Celular Tumoral , Sulfonamidas/farmacologia , Sulfonamidas/química , Ratos , Descoberta de Drogas
9.
Medicine (Baltimore) ; 103(18): e38024, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701268

RESUMO

BACKGROUND: This study aimed to investigate whether lower limb joints mutually compensate for each other, resulting in motor synergy that suppresses toe vertical position fluctuation, and whether walking speeds affect lower limb synergy. METHODS: Seventeen male university students walked at slow (0.85 ±â€…0.04 m/s), medium (1.43 ±â€…0.05 m/s) and fast (1.99 ±â€…0.06 m/s) speeds on a 15-m walkway while lower limb kinematic data were collected. Uncontrolled manifold analysis was used to quantify the strength of synergy. Two-way (speed × phase) repeated-measures analysis of variance was used to analyze all dependent variables. RESULTS: A significant speed-by-phase interaction was observed in the synergy index (SI) (P  < .001). At slow walking speeds, subjects had greater SI during mid-swing (P  < .001), while at fast walking speeds, they had greater SI during early-swing (P  < .001). During the entire swing phase, fast walking exhibited lower SI values than medium (P  = .005) and slow walking (P  = .027). CONCLUSION: Kinematic synergy plays a crucial role in controlling toe vertical position during the swing phase, and fast walking exhibits less synergy than medium and slow walking. These findings contribute to a better understanding of the role of kinematic synergy in gait stability and have implications for the development of interventions aimed at improving gait stability and reducing the risk of falls.


Assuntos
Extremidade Inferior , Dedos do Pé , Velocidade de Caminhada , Humanos , Masculino , Fenômenos Biomecânicos , Adulto Jovem , Velocidade de Caminhada/fisiologia , Extremidade Inferior/fisiologia , Dedos do Pé/fisiologia , Marcha/fisiologia , Caminhada/fisiologia , Adulto
10.
Artigo em Inglês | MEDLINE | ID: mdl-38767715

RESUMO

Subjective well-being (SWB) is an important measure for mental health status. Previous research has shown that physical activity can affect an individual's well-being, yet the underlying molecular mechanism remains to be clarified. In this study, we aim to evaluate the potential interactions between mitochondrial genes and physical activity (PA) as well as their combined effects on individual well-being. SWB phenotype data in UK Biobank were enrolled for this study including nine aspects such as work/job satisfaction, health satisfaction, family relationship satisfaction, friendships satisfaction, financial situation satisfaction, ever depressed for a whole week, general happiness, general happiness with own health and belief that own life is meaningful. We made analysis for each aspects separately. Firstly, mitochondria-wide association studies (MiWAS) was conducted to assess the association of mitochondrial Single Nucleotide Polymorphisms SNP with each aspect of SWB. Then an interaction analysis of mitochondrial DNA (mtDNA) mutation and PA was performed to evaluate their joint effect on SWB status. Meanwhile, these two analysis were made for female and male group separately as well as the total samples, all under the control of possible confounding factors including gender, age, Townsend Deprivation Index (TDI), education, alcohol consumption, smoking habits, and 10 principal components. MiWAS analysis identified 45 mtSNPs associated with 9 phenotypes of SWB. For example, m.15218A > G on MT-CYB in the health satisfaction phenotype of the total subjects. Gender-specific analyses found 30 mtSNPs in females and 58 in males, involving 13 mtGenes. In mtDNA-PA interaction analysis, we also identified 10 significant mtDNA-PA interaction sets for SWB. For instance, m.13020 T > C (MT-ND5) was associated with the SWB financial situation satisfaction phenotype in all subjects (P = 0.00577). In addition, MiWAS analysis identified 12 mtGene variants associated with SWB, as MT-ND1 and MT-ND2. However, in mtDNA-PA interactions we detected 7 mtDNA affecting psychiatric disorders occurring, as in the friendships satisfaction phenotype (m.3394 T > C on MT-ND1). Our study results suggest an implication of the interaction between mitochondrial function and physical activity in the risk of psychiatric disorder development.

11.
Head Face Med ; 20(1): 31, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745246

RESUMO

BACKGROUND: In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. METHODS: A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case-control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. RESULTS: A significant decrease in ANB (P < 0.05 for both groups), the retraction and uprighting of the maxillary and mandibular incisors, and the retraction of protruded upper and lower lips were observed in both groups. Moreover, a significant intrusion of the maxillary molars was observed via the cephalometric analysis (- 1.56 ± 1.52 mm, P < 0.05) and cast superimposition (- 2.25 ± 1.03 mm, P < 0.05) of the MMA + VC group but not the MMA group, which resulted in a remarkable decrease in the mandibular plane angle (- 1.82 ± 1.38°, P < 0.05). The Z angle (15.25 ± 5.30°, P < 0.05) and Chin thickness (- 0.97 ± 0.45°, P < 0.05) also improved dramatically in the MMA + VC group, indicating a better profile and a relaxed mentalis. Multivariate regression showed that the improvement in the soft tissue was closely related to the counterclockwise rotation of the mandible plane (P < 0.05). CONCLUSIONS: TAD-assisted vertical control can achieve intrusion of approximately 2 mm for the upper first molars and induce mandibular counterclockwise rotation of approximately 1.8°. Moreover, it is especially important for patients without sufficient retraction of the upper incisors or a satisfactory chin shape.


Assuntos
Cefalometria , Má Oclusão Classe II de Angle , Humanos , Má Oclusão Classe II de Angle/terapia , Má Oclusão Classe II de Angle/diagnóstico por imagem , Feminino , Masculino , Estudos Retrospectivos , Adulto , Estudos de Casos e Controles , Adulto Jovem , Resultado do Tratamento , Procedimentos de Ancoragem Ortodôntica/métodos , Procedimentos de Ancoragem Ortodôntica/instrumentação , Ortodontia Corretiva/métodos , Técnicas de Movimentação Dentária/métodos , Dimensão Vertical , Adolescente
12.
Neuroscience ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734302

RESUMO

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia-reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.

13.
Cureus ; 16(4): e57650, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38689674

RESUMO

This case report presents a rare instance of Eruptive Pruritic Papular Porokeratosis (EPPP) in a 71-year-old Chinese male, emerging on atypical sites (face, scalp, and ears) following a COVID-19 infection, and explores the potential link between viral infections and EPPP onset. The patient's lesions, characterized by annular brown patches with hyperkeratotic ridges, showed significant improvement following treatment with Baricitinib and Acitretin. This case underscores the need for awareness of unusual presentations of EPPP and suggests the potential efficacy of Janus Kinase (JAK) inhibitors in treatment, prompting further research into the pathophysiological connections between EPPP and viral infections. Adherence to the SCARE 2023 guidelines ensures a comprehensive and transparent case presentation.

14.
Angew Chem Int Ed Engl ; : e202404186, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691059

RESUMO

The introduction of nitrogen-containing functional groups to chiral polymer backbones enables the tailoring of physical properties and offers opportunities for further post-polymerization modification. However, the substrate scope of such polymers is extremely limited because monomers having nitrogen-containing groups can change coordination state with respect to the metal centers, thus decreasing the activity and enantioselectivity and even poisoning the catalyst completely. In this paper, we report our attempts to carry out the asymmetric copolymerization of meso-epoxide with highly reactive isocyanates. In particular, we found that biphenol-linked bimetallic Co(III) complexes with multiple chiral centers are very efficient in catalyzing this asymmetric copolymerization reaction, affording optically active polyurethanes with a completely alternating nature and a high enantioselectivity of up to 94% ee. Crucially, we identified that the steric hindrance at the phenolate ortho position of the ligand strongly influences the catalytic activity and product enantioselectivity. In addition, density functional theory calculations revealed that the highly sterically bulky substituents change the mechanism from bimetallic to monometallic, and result in the unexpected inversion of the chiral induction direction. Moreover, the high stereoregularity of the produced polyurethanes enhances their thermal stability. This study offers a versatile methodology for the synthesis of chiral polymers containing nitrogen functionalities.

15.
J Gerontol Nurs ; 50(5): 43-49, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38691116

RESUMO

PURPOSE: To explore care requirements of older adults with urinary incontinence (UI) and contributing factors. METHOD: This cross-sectional study used the Older Adults Urinary Incontinence Care Needs Inventory to survey participants with UI in three large-scale tertiary hospitals located in Guangzhou City, China, from January 2023 to November 2023. Statistical analyses, including analysis of variance, t tests, correlation analyses, and linear regression models, were conducted to assess factors influencing participants' care needs. RESULTS: A total of 530 older adults with UI participated in the survey and mean standardized score for overall care needs was 78.65 (SD = 5.01), with mean scores for each dimension ranging from 70.88 (SD = 10.55) for social participation needs to 82.45 (SD = 7.11) for health education needs. Factors that were found to influence incontinence care needs in older adults included age, literacy level, number of leaks, and type of disease (F = 37.07, adjusted R2 = 0.290, p < 0.001). CONCLUSION: Comprehensive care for older adults with UI, encompassing physiological, psychological, and social aspects, is crucial. It is essential to tailor care to individual needs and characteristics, taking into account factors, such as age and education, to ensure effective care. [Journal of Gerontological Nursing, 50(5), 43-49.].


Assuntos
Incontinência Urinária , Humanos , Incontinência Urinária/enfermagem , Estudos Transversais , Idoso , Feminino , Masculino , Idoso de 80 Anos ou mais , China , Pessoa de Meia-Idade , Inquéritos e Questionários , Avaliação das Necessidades , Necessidades e Demandas de Serviços de Saúde
16.
Adv Sci (Weinh) ; : e2306348, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696655

RESUMO

Patients who have non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations are more prone to brain metastasis (BM) and poor prognosis. Previous studies showed that the tumor microenvironment of BM in these patients is immunosuppressed, as indicated by reduced T-cell abundance and activity, although the mechanism of this immunosuppression requires further study. This study shows that reactive astrocytes play a critical role in promoting the immune escape of BM from EGFR-mutated NSCLC by increasing the apoptosis of CD8+ T lymphocytes. The increased secretion of interleukin 11(IL11) by astrocytes promotes the expression of PDL1 in BM, and this is responsible for the increased apoptosis of T lymphocytes. IL11 functions as a ligand of EGFR, and this binding activates EGFR and downstream signaling to increase the expression of PDL1, culminating in the immune escape of tumor cells. IL11 also promotes immune escape by binding to its intrinsic receptor (IL11Rα/glycoprotein 130 [gp130]). Additional in vivo studies show that the targeted inhibition of gp130 and EGFR suppresses the growth of BM and prolongs the survival time of mice. These results suggest a novel therapeutic strategy for treatment of NSCLC patients with EGFR mutations.

17.
Adv Mater ; : e2402322, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718226

RESUMO

Novel strategies to facilitate tumor-specific drug delivery and restore immune attacks remain challenging in overcoming the current limitations of chemoimmunotherapy. An antitumor chemoimmunotherapy system comprising bioorthogonal reaction-ready group tetrazine (TZ) modified with an anti-PD-L1 antibody (αPD-L1TZ) and TZ-activatable prodrug vinyl ether-doxorubicin (DOX-VE) for self-reinforced anti-tumor chemoimmunotherapy is proposed. The αPD-L1TZ effectively disrupts the PD-L1/PD-1 interaction and activates the DOX prodrug in situ through the bioorthogonal click reaction of TZ and VE. Conversely, the activated DOX upregulates PD-L1 on the surface of tumor cells, facilitating tumor accumulation of αPD-L1TZ and enhancing DOX-VE activation. Furthermore, the activated DOX-induced immunogenic cell death of tumor cells, substantially improving the response efficiency of αPD-L1 in an immune-suppressive tumor microenvironment. Thus, PD-L1 blocking and bioorthogonal in situ prodrug activation synergistically enhance the antitumor efficacy of the chemoimmunotherapy system. Therefore, the system significantly enhances αPD-L1 tumor accumulation and prodrug activation and induces a robust immunological memory effect to prevent tumor recurrence and metastasis. Thus, a feasible chemoimmunotherapy combination regimen is presented.

18.
Zhongguo Zhen Jiu ; 44(5): 521-5, 2024 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-38764101

RESUMO

OBJECTIVE: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) for alleviating postoperative cough in lung cancer patients undergoing video-assisted thoracoscopic surgery. METHODS: A total of 110 patients with lung cancer undergoing video-assisted thoracoscopic surgery were randomly divided into a TEAS group (55 cases, 2 cases dropped out) and a sham-TEAS group (55 cases, 4 cases dropped out). In the TEAS group, TEAS was delivered 30 min before anesthesia and on day 1 to day 4 after operation separately, with disperse-dense wave, in frequence of 2 Hz/100 Hz. The acupoints included Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Hegu (LI 4), Lieque (LU 7) and Taixi (KI 3) on the both sides. In the sham-TEAS group, at the same time points and same acupoints as the TEAS group, the electrode pads were attached to the acupoints, but without electric stimulation. The interventions were given 30 min each time, once daily in the two groups. The incidence of cough and the scores of visual analogue scale (VAS) for cough on the first day (T1), the third day (T2), the fifth day (T3), 1 month (T4) and 3 months (T5) after operation, as well as the scores of the Leicester cough questionnaire (LCQ) on T4 and T5 were compared between the two groups; the contents of serum C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were detected before surgery (T0) and at T1, T2 and T3. The first flatus time, the first defecation time, the first ambulation time, the postoperative hospital day and the incidence of postoperative nausea and vomiting were compared between the two groups. RESULTS: Compared with the sham-TEAS group, the cough incidence at T3 and cough VAS scores at T1 to T5 were lower in the TEAS group (P<0.05, P<0.01), and the LCQ scores at T4 and T5 were higher (P<0.05). The serum contents of CRP, IL-6 and TNF-αat T1 to T3 in the TEAS group were lower than those of the sham-TEAS group (P<0.01). The first flatus time, the first defecation time and the first ambulation time were earlier (P<0.05, P<0.01); and the postoperative hospital day was shorter (P<0.05) and the incidence of postoperative nausea and vomiting was lower (P<0.05) in the TEAS group when compared with those of the sham-TEAS group. CONCLUSION: TEAS relieves cough in lung cancer patients undergoing video-assisted thoracoscopic surgery, improves quality of life and promotes the early postoperative recovery.


Assuntos
Pontos de Acupuntura , Tosse , Neoplasias Pulmonares , Complicações Pós-Operatórias , Cirurgia Torácica Vídeoassistida , Estimulação Elétrica Nervosa Transcutânea , Humanos , Masculino , Tosse/etiologia , Tosse/terapia , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/cirurgia , Idoso , Adulto , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/etiologia , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Proteína C-Reativa/metabolismo
19.
Adv Healthc Mater ; : e2400517, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760889

RESUMO

Photoacoustic imaging (PAI) can sensitively detect regions and substances with strong optical absorption, which means that diseased tissue can be imaged with high contrast in the presence of surrounding healthy tissue through the photoacoustic effect. However, its signal intensity and resolution may be limited by background signals generated by endogenous chromophores such as melanin and hemoglobin. A feasible method for practical application of this so-called background-suppressed PAI is still lacking. In this work, we develop a dual-wavelength differential background noise suppressed photoacoustic tomography based on organic semiconducting polymer dots (Pdots). The Pdots have a strong absorption peak at 945 nm, and then the absorption decreases sharply with the increase of wavelength, and the absorption intensity drops to only about a quarter of the original value at 1050 nm. The present system significantly suppresses the strong background noise of blood through dual-wavelength differential PAI, enabling precise monitoring of the distribution information of theranostic agents in diseased tissues. The signal-to-noise ratio of the theranostic agent distribution map is increases by about 20 dB. This work provides a platform for real-time and accurate monitoring of tumors and drugs, which helps avoid damage to healthy tissue during treatment and has clinical significance in cancer treatment. This article is protected by copyright. All rights reserved.

20.
Exp Cell Res ; 438(1): 114037, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631545

RESUMO

Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.


Assuntos
Adenocarcinoma de Pulmão , Anoikis , Neoplasias Pulmonares , Humanos , Anoikis/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Prognóstico , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Apoptose/genética
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