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1.
JAMA Netw Open ; 7(4): e245295, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38625704

RESUMO

Importance: Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. Objective: To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. Design, Setting, and Participants: This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Exposures: Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. Main Outcomes and Measures: The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. Results: This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. Conclusions and Relevance: In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Pessoa de Meia-Idade , Idoso , Grupos Raciais , Etnicidade
2.
Molecules ; 29(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38611836

RESUMO

As a traditional Chinese medicine, Salvia miltiorrhiza Bunge was first recorded in the Shennong Materia Medica Classic and is widely used to treat "the accumulation of symptoms and masses". The main active ingredient of Salvia miltiorrhiza Bunge, Tanshinone IIA (TIIA), has shown anti-inflammatory, antitumor, antifibrosis, antibacterial, and antioxidative activities, etc. In this study, the results showed that TIIA could inhibit the proliferation and migration of HepG2 cells and downregulate glutathione (GSH) and Glutathione Peroxidase 4 (GPX4) levels; besides, TIIA induced the production of Reactive Oxygen Species (ROS), and upregulated the total iron content. Based on network pharmacology analysis, the antitumor effect of TIIA was found to be focused on the endoplasmic reticulum (ER)-mediated ferroptosis signaling pathway, with protein kinase R (PKR)-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-heat shock 70 kDa protein 5 (HSPA5) as the main pathway. Herein, TIIA showed typical ferroptosis characteristics, and a ferroptosis inhibitor (ferrostatin-1) was used to verify the effect. The antitumor effects of TIIA, occurring through the inhibition of the PERK-ATF4-HSPA5 pathway, were further observed in vivo as significantly inhibited tumor growth and the improved pathological morphology of tumor tissue in H22-bearing mice. In summary, the antitumor mechanism of TIIA might be related to the downregulation of the activation of PERK-ATF4-HSPA5 pathway-mediated ferroptosis.


Assuntos
Fator 4 Ativador da Transcrição , Ferroptose , Animais , Camundongos , Fator 4 Ativador da Transcrição/genética , Chaperona BiP do Retículo Endoplasmático , Abietanos/farmacologia , Glutationa
3.
Fitoterapia ; 175: 105946, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38575087

RESUMO

Four compounds (1-4) featuring with an L-rhodinose and spiroketal, possess uncommon continuous hydroxy groups in the macrolide skeleton, and a dichloro-diketopiperazine (5) were isolated from a marine derived Micromonospora sp. FIMYZ51. The determination of the relative and absolute configurations of all isolates was achieved by extensive spectroscopic analyses, single-crystal X-ray diffraction analysis, and ECD calculations. According to structural characteristic and genomic sequences, a plausible biosynthetic pathway for compound 1-4 was proposed and a spirocyclase was inferred to be responsible for the formation of the rare spirocyclic moiety. Compounds 1-4 exhibited potent antifungal activities which is equal to itraconazole against Aspergillus niger. Compounds 1-5 exhibited different degree of inhibitory activities against opportunistic pathogenic bacteria of endocarditis (Micrococcus luteus) with MIC values ranging from 0.0625 µg/mL to 32 µg/mL. Compounds 2 and 3 showed moderate cytotoxicity against drug-resistant tumor cell lines (Namalwa and U266). The result not only provides active lead-compounds, but also reveal the potential of the spirocyclase gene resources from Micromonospora sp., which highlights the promising potential of the strain for biomedical applications.

4.
Phys Med Biol ; 69(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38640915

RESUMO

Objective. Beam hardening (BH) artifacts in computed tomography (CT) images originate from the polychromatic nature of x-ray photons. In a CT system with a bowtie filter, residual BH artifacts remain when polynomial fits are used. These artifacts lead to worse visuals, reduced contrast, and inaccurate CT numbers. This work proposes a pixel-by-pixel correction (PPC) method to reduce the residual BH artifacts caused by a bowtie filter.Approach. The energy spectrum for each pixel at the detector after the photons pass through the bowtie filter was calculated. Then, the spectrum was filtered through a series of water slabs with different thicknesses. The polychromatic projection corresponding to the thickness of the water slab for each detector pixel could be obtained. Next, we carried out a water slab experiment with a mono energyE= 69 keV to get the monochromatic projection. The polychromatic and monochromatic projections were then fitted with a 2nd-order polynomial. The proposed method was evaluated on digital phantoms in a virtual CT system and phantoms in a real CT machine.Main results. In the case of a virtual CT system, the standard deviation of the line profile was reduced by 23.8%, 37.3%, and 14.3%, respectively, in the water phantom with different shapes. The difference of the linear attenuation coefficients (LAC) in the central and peripheral areas of an image was reduced from 0.010 to 0.003cm-1and 0.007cm-1to 0 in the biological tissue phantom and human phantom, respectively. The method was also validated using CT projection data obtained from Activion16 (Canon Medical Systems, Japan). The difference in the LAC in the central and peripheral areas can be reduced by a factor of two.Significance. The proposed PPC method can successfully remove the cupping artifacts in both virtual and authentic CT images. The scanned object's shapes and materials do not affect the technique.


Assuntos
Artefatos , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas , Tomografia Computadorizada por Raios X , Tomografia Computadorizada por Raios X/métodos , Processamento de Imagem Assistida por Computador/métodos , Humanos
5.
Adv Sci (Weinh) ; 11(17): e2306076, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38445883

RESUMO

Earthworms, long utilized in traditional medicine, serve as a source of inspiration for modern therapeutics. Lysenin, a defensive factor in the coelom fluid of the earthworm Eisenia fetida, has multiple bioactivities. However, the inherent toxicity of Lysenin as a pore-forming protein (PFP) restricts its application in therapy. Here, a gene therapy strategy based on Lysenin for cancer treatment is presented. The formulation consists of polymeric nanoparticles complexed with the plasmid encoding Lysenin. After transfection in vitro, melanoma cells can express Lysenin, resulting in necrosis, autophagy, and immunogenic cell death. The secretory signal peptide alters the intracellular distribution of the expressed product of Lysenin, thereby potentiating its anticancer efficacy. The intratumor injection of Lysenin gene formulation can efficiently kill the transfected melanoma cells and activate the antitumor immune response. Notably, no obvious systemic toxicity is observed during the treatment. Non-viral gene therapy based on Lysenin derived from Eisenia foetida exhibits potential in cancer therapy, which can inspire future cancer therapeutics.


Assuntos
Terapia Genética , Melanoma , Oligoquetos , Animais , Camundongos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Terapia Genética/métodos , Melanoma/terapia , Melanoma/genética , Nanopartículas/química , Oligoquetos/genética , Toxinas Biológicas/genética , Feminino , Humanos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38551437

RESUMO

Objective: To investigate the effect of the intervention program based on the Interaction Model of Client Health Behavior (IMCHB) in patients with pressure injury (PI). Methods: The First Affiliated Hospital of Qiqihar Medical University received thirty patients suspected of having pressure injuries from June to December 2022. These patients were selected as the control group. Another thirty patients suspected of having pressure injuries were received by the hospital from January to June 2023 and were selected as the experimental group. The experimental group received a usual care protocol, while the trial group received the IMCHB model intervention for three months. The study compared the knowledge of pressure injuries, quality of life, incidence of pressure injuries, and patient satisfaction of high-risk patients between the two groups. Results: After the intervention, the PI awareness score of caregivers in the experimental group was (31.90 ± 5.24). It is higher than the control group (26.37 ± 6.85). The point of social function, physical function and material function of experimental group were (57.03 ± 5.32), (33.47 ± 3.52) and (58.53 ± 6.93). Respectively, it was higher than the experimental group (48.63 ± 4.80), (27.17 ± 3.04), (46.13 ± 6.72). The incidence of high-risk PI in the experimental group was 3.33%. The point of the control group was 26.67%. The total satisfaction of the experimental group was (8.27 ± 0.78) points, higher than the control group (7.30 ± 0.65). The difference was of statistical significance (P < .05). Conclusion: The intervention program based on IMCHB can significantly improve cognitive ability and thus promote health behavior.

7.
Postepy Dermatol Alergol ; 41(1): 66-71, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38533362

RESUMO

Introduction: Melasma is an acquired hypermelanosis and occurs in areas exposed to sunlight. Aim: To investigate the effectiveness of Danggui Shaoyao powder (DSP) as a complementary drug in the treatment of melasma. Material and methods: A total of 40 melasma patients over the age of 18 who met the inclusion criteria entered the study randomly in two DSP + Hydroquinone (DSP + H) and Hydroquinone (H) groups. Results: At the beginning of the study, the average MASI score of the two groups of patients had no statistical difference (DSP + H: 15.79 ±1.01 vs. H: 15.37 ±1.17, p = 0.23). But from the eighth week of treatment, the MASI score of the patients decreased significantly and in the DSP + H group it decreased statistically significantly compared to the H group (DSP + H: 5.83 ±0.97 vs. H: 8.29 ±2.23, p < 0.001 for the eighth week and DSP + H: 3.60 ±0.58 vs. H: 5.52 ±1.73, p < 0.001 for the twelfth week of the treatment). It means after 12 weeks of treatment, the average MASI score of patients in the DSP + H group decreased by 77.26 ±2.70%, but in the grroup H, it decreased by 64.31 ±9.68% (p < 0.001). Dynamic PGA showed that excellent treatment occurred in 65% of the + H group H, but only 20% of the H group (p = 0.01). Conclusions: Oral DSP for 12 weeks along with hydroquinone cream can significantly reduce the MASI score of melasma patients and increase the patients' recovery and satisfaction.

8.
Adv Healthc Mater ; : e2400071, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501563

RESUMO

The treatment of infected wounds remains a challenging biomedical problem. Some bioactive small-molecule hydrogelators with unique rigid structures can self-assemble into supramolecular hydrogels for wound healing. However, they are still suffered from low structural stability and bio-functionality. Herein, a supramolecular hydrogel antibacterial dressing with a dual nanofibrillar network structure is proposed. A nanofibrillar network created by a small-molecule hydrogelator, puerarin extracted from the traditional Chinese medicine Pueraria, is interconnected with a secondary macromolecular silk fibroin nanofibrillar network induced by Ga ions via charge-induced supramolecular self-assembly. The resulting hydrogel features adequate mechanical strength for sustainable retention at wounds. Good biocompatibility and efficient bacterial inhibition are obtained when the Ga ion concentration is 0.05%. Otherwise, the substantial release of Ga ions and puerarin endows the hydrogel with excellent hemostatic and antioxidative properties. In vivo, evaluation of a mouse-infected wound model demonstrates that its healing effect outperformed that of a commercially available silver-containing wound dressing. The experimental group successfully achieves a 100% wound closure rate on day 10. This study sheds new light on the design of nanofibrillar hydrogels based on supramolecular self-assembly of naturally derived bioactive molecules as well as their clinical use for treating chronic infected wounds.

9.
Int J Biol Macromol ; 264(Pt 2): 130785, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471605

RESUMO

Chemotherapy remains one of the most widely used cancer treatment modalities in clinical practice. However, the characteristic microenvironment of solid tumors severely limits the anticancer efficacy of chemotherapy. In addition, a single treatment modality or one death pathway reduces the antitumor outcome. Herein, tumor-targeting O2 self-supplied nanomodules (CuS@DOX/CaO2-HA) are proposed that not only alleviate tumor microenvironmental hypoxia to promote the accumulation of chemotherapeutic drugs in tumors but also exert photothermal effects to boost drug release, penetration and combination therapy. CuS@DOX/CaO2-HA consists of copper sulfide (CuS)-loaded calcium peroxide (CaO2) and doxorubicin (DOX), and its surface is further modified with HA. CuS@DOX/CaO2-HA underwent photothermal treatment to release DOX and CaO2. Hyperthermia accelerates drug penetration to enhance chemotherapeutic efficacy. The exposed CaO2 reacts with water to produce Ca2+, H2O2 and O2, which sensitizes cells to chemotherapy through mitochondrial damage caused by calcium overload and a reduction in drug efflux via the alleviation of hypoxia. Moreover, under near infrared (NIR) irradiation, CuS@DOX/CaO2-HA initiates a pyroptosis-like cell death process in addition to apoptosis. In vivo, CuS@DOX/CaO2-HA demonstrated high-performance antitumor effects. This study provides a new strategy for synergistic enhancement of chemotherapy in hypoxic tumor therapy via combination therapy and multiple death pathways.


Assuntos
Nanopartículas , Neoplasias , Humanos , Ácido Hialurônico/uso terapêutico , Peróxido de Hidrogênio , Doxorrubicina , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fototerapia , Hipóxia , Linhagem Celular Tumoral , Microambiente Tumoral
10.
Phytomedicine ; 126: 155222, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382279

RESUMO

BACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-ß-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.


Assuntos
Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Camundongos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Farmacologia em Rede , Metabolômica/métodos , Medicina Tradicional Chinesa/métodos , Nefropatias Diabéticas/tratamento farmacológico , Aminoácidos
11.
Phytomedicine ; 125: 155343, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290230

RESUMO

BACKGROUND: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barré syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs. Atranorin is a lichen secondary metabolite with a wide range of biological activities, including anti-inflammatory, antibacterial and antioxidant, etc. However, the antiviral activity of atranorin and underlying mechanism has not been fully elucidated. PURPOSE: We aimed to determine the anti-ZIKV activity of atranorin in human glioma cell line SNB-19 and investigate the potential mechanism from the perspective of viral life cycle and the host cell functions. METHODS: We first established ZIKV-infected human glioma cells (SNB-19) model and used Western Blot, RT-qPCR, immunofluorescence, fluorescence-activated cell sorting (FACS) and plaque assay to evaluate the anti-ZIKV activity of atranorin. Then we assessed the regulation effect of atranorin on ZIKV induced IFN signal pathway activation by RT-qPCR. Afterward, we introduced time-of-addition assay, viral adsorption assay, viral internalization assay and transferrin uptake assay to define which step of ZIKV lifecycle is influenced by atranorin. Finally, we performed virus infectivity assay, molecular docking and thermal shift assay to uncover the target protein of atranorin on ZIKV. RESULTS: Our study showed that atranorin could protect SNB-19 cells from ZIKV infection, as evidenced by inhibited viral protein expression and progeny virus yield. Meanwhile, atranorin attenuated the activation of IFN signal pathway and downstream inflammatory response that induced by ZIKV infection. The results of time-of-addition assay indicated that atranorin acted primarily by disturbing the viral entry process. After ruling out the effect of atranorin on AXL receptor tyrosine kinase (AXL) dependent virus adsorption and clathrin-mediated endocytosis, we confirmed that atranorin directly targeted the viral envelope protein and lowered ZIKV infectivity by thermal shift assay and virus infectivity assay respectively. CONCLUSION: We found atranorin inhibits ZIKV infection in SNB-19 cells via targeting ZIKV envelope protein. Our study provided an experimental basis for the further development of atranorin and a reference for antiviral drug discovery from natural resources.


Assuntos
Glioblastoma , Hidroxibenzoatos , Infecção por Zika virus , Zika virus , Animais , Recém-Nascido , Humanos , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/metabolismo , Zika virus/fisiologia , Proteínas do Envelope Viral , Glioblastoma/tratamento farmacológico , Simulação de Acoplamento Molecular , Replicação Viral , Linhagem Celular
12.
Medicine (Baltimore) ; 103(4): e36653, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277544

RESUMO

BACKGROUND: Previous clinical trials have reported that acupoint catgut embedding (ACE) is a useful modality for weight loss. However, no study has specifically investigated the effectiveness and safety of comparing verum and sham ACE in adults with obesity. Thus, this study aimed to evaluate the effectiveness and safety of comparing verum and sham ACE in obese adults. METHODS: A comprehensive literature search was conducted in the electronic databases of PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and China Biomedical Literature Service System from inception to April 1, 2022. Randomized clinical trials that focused on evaluating the effectiveness of comparing verum and sham ACE in adults with obesity were included. The primary outcomes included reduction in body weight, body mass index, hip circumference, and waist circumference. The secondary outcomes consisted of a decrease in body fat percentage and the occurrence rate of adverse events. The methodological quality of the included randomized clinical trials was evaluated using the Cochrane Risk-of-bias tool. Statistical analysis was performed using RevMan 5.4 software. RESULTS: Six trials involving 679 adults with obesity were included in this study and entered in the data analysis of systematic review and meta-analysis. Results of the meta-analysis revealed significant reduction in body weight (mean difference [MD] = -1.68, 95% confidence intervals (CI) [-2.34, -1.01], I2 = 51%, P < .001), body mass index (MD = -0.51, 95% CI [-0.81, -0.21], I2 = 74%, P < .001), hip circumference (MD = -1.11, 95% CI [-1.67, -0.55], I2 = 0%, P < .001), waist circumference (MD = -2.42, 95% CI [-3.38, -1.45], I2 = 68%, P < .001), and decrease in body fat percentage (MD = -0.83, 95% CI [-1.30, -0.36], I2 = 16%, P < .001) in comparing verum and sham ACE. However, no significant difference was identified in AEs (odds ratio = 1.53, 95% CI [0.80, 2.95], I2 = 0%, P = .20) between the 2 groups. CONCLUSION: ACE is effective in the treatment of obesity in adults with safety profile. Further studies with higher quality and larger sample size are warranted to confirm the current findings.


Assuntos
Pontos de Acupuntura , Categute , Adulto , Humanos , Categute/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade/tratamento farmacológico , Peso Corporal
13.
Adv Healthc Mater ; 13(10): e2303432, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38069831

RESUMO

Small molecular organic optical agents with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), hold credible promise for anti-tumor therapy by overcoming individual drawbacks and enhancing photon utilization efficiency. However, developing effective dual-function PTT-PDT photosensitizers (PSs) for efficient synergistic phototherapy remains challenging. Here, a benz[c,d]indolium-substituted hemicyanine named Rh-BI, which possesses a high photothermal conversion efficiency of 41.67% by exhaustively suppressing fluorescence emission, is presented. Meanwhile, the rotating phenyl group at meso-site induces charge recombination to enhance the molar extinction coefficient up to 13.58 × 104 M-1cm-1, thereby potentiating the photodynamic effect. Under 808 nm irradiation, Rh-BI exhibits significant phototoxicity in several cancer cell types in vitro with IC50 values as low as ≈0.5 µM. Moreover, treatment of 4T1 tumor-bearing mice with Rh-BI under laser irradiation successfully inhibits tumor growth. In a word, an effective strategy is developed to build PTT-PDT dual-functional optical materials based on hemicyanine backbone for tumor therapy by modulating conjugation system interaction to adjust the energy consumption pathway.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Fototerapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Carbocianinas/uso terapêutico , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
14.
Adv Sci (Weinh) ; 11(7): e2307051, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063804

RESUMO

The plant hormone salicylic acid (SA) plays critical roles in plant innate immunity. Several SA derivatives and associated modification are identified, whereas the range and modes of action of SA-related metabolites remain elusive. Here, the study discovered 2,4-dihydroxybenzoic acid (2,4-DHBA) and its glycosylated form as native SA derivatives in plants whose accumulation is largely induced by SA application and Ps. camelliae-sinensis (Pcs) infection. CsSH1, a 4/5-hydroxylase, catalyzes the hydroxylation of SA to 2,4-DHBA, and UDP-glucosyltransferase UGT95B17 catalyzes the formation of 2,4-DHBA glucoside. Down-regulation reduced the accumulation of 2,4-DHBA glucosides and enhanced the sensitivity of tea plants to Pcs. Conversely, overexpression of UGT95B17 increased plant disease resistance. The exogenous application of 2,4-DHBA and 2,5-DHBA, as well as the accumulation of DHBA and plant resistance comparison, indicate that 2,4-DHBA functions as a potentially bioactive molecule and is stored mainly as a glucose conjugate in tea plants, differs from the mechanism described in Arabidopsis. When 2,4-DHBA is applied exogenously, UGT95B17-silenced tea plants accumulated more 2,4-DHBA than SA and showed induced resistance to Pcs infection. These results indicate that 2,4-DHBA glucosylation positively regulates disease resistance and highlight the role of 2,4-DHBA as potentially bioactive molecule in the establishment of basal resistance in tea plants.


Assuntos
Arabidopsis , Camellia sinensis , Catecóis , Hidroxibenzoatos , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Camellia sinensis/metabolismo , Resistência à Doença , Arabidopsis/metabolismo , Chá/metabolismo
15.
Plant Physiol ; 194(3): 1527-1544, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-37882637

RESUMO

Phosphorus (P) plays a pivotal role in plant growth and development. Low P stress can greatly hamper plant growth. Here, we identified a QTL (named QPH-9-1), which is associated with P efficiency across multiple environments through linkage analysis and genome-wide association study. Furthermore, we successfully cloned the underlying soybean (Glycine max) gene GmRR1 (a soybean type-B Response Regulator 1) that encodes a type-B response regulator protein. Knockout of GmRR1 resulted in a substantial increase in plant height, biomass, P uptake efficiency, and yield-related traits due to the modification of root structure. In contrast, overexpression of GmRR1 in plants resulted in a decrease in these phenotypes. Further analysis revealed that knockout of GmRR1 substantially increased the levels of auxin and ethylene in roots, thereby promoting root hair formation and growth by promoting the formation of root hair primordium and lengthening the root apical meristem. Yeast two-hybrid, bimolecular fluorescence complementation, and dual-luciferase assays demonstrated an interaction between GmRR1 and Histidine-containing Phosphotransmitter protein 1. Expression analysis suggested that these proteins coparticipated in response to low P stress. Analysis of genomic sequences showed that GmRR1 underwent a selection during soybean domestication. Taken together, this study provides further insights into how plants respond to low P stress by modifying root architecture through phytohormone pathways.


Assuntos
Glycine max , Raízes de Plantas , Raízes de Plantas/metabolismo , Glycine max/genética , Fósforo/metabolismo , Estudo de Associação Genômica Ampla , Meristema/metabolismo
16.
Eur J Neurosci ; 59(2): 192-207, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38145884

RESUMO

Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.


Assuntos
Eletroacupuntura , Traumatismos dos Nervos Periféricos , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Traumatismos dos Nervos Periféricos/terapia , Fibras Musculares Esqueléticas , Músculo Esquelético , Nervo Isquiático/lesões , Atrofia Muscular/terapia , Proteínas Quinases p38 Ativadas por Mitógeno
17.
J Subst Use Addict Treat ; 156: 209189, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37866441

RESUMO

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.


Assuntos
Depressão , Estimulação Magnética Transcraniana , Humanos , Ansiedade/terapia , Depressão/terapia , Comportamento Impulsivo , Ritmo Teta/fisiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-38064600

RESUMO

Background: Artificial joint replacement has become one of the most effective means for the clinical treatment of senile degenerative end-stage bone and joint diseases. All complications were directly or indirectly related to bleeding, and low body temperature can lead to bleeding, which have been a conceren in rthroplasty for elderly patients. Methods: The computer retrieves eight databases, including Cochrane Library, PubMed, EMbase, Web of Science, CNKI, China Biomedical Literature Database (CBM), VIP and WanFang, to obtain controlled trials at home and abroad on the effects of body temperature protection on intraoperative bleeding in elderly patients undergoing arthroplasty. The search term is "temperature", "bleeding," and "arthroplasty". The search time was from the establishment of the library until February 2022. The literature screening results were obtained by reading the full text, and the process was completed independently by 2 researchers.After a rigorous literature quality evaluation, data analysis was performed using RevMan 5.3 software. Results: 9 studies were ultimately included in this meta-analysis. 8 studies reported the blood loss of the test group and the control group. Meta-analysis showed that the blood loss of the test group was significantly lower (SMD: -45.09; 95% Cl: -67.76, -22.43; P < .01) than the control group. 44 studies showed that the Number of blood transfusions of the experimental group was significantly lower than the control group (OR:0.60; 95% Cl: 0.39,0.92; P = .01). 3 studies showed that the intraoperative temperature of the experimental group was significantly higher than the control group (SMD:0.60; 95% Cl: 0.20,0.99; P = .003). 4 studies showed that the postoperative temperature of the test group was significantly higher than the control group (SMD: 0.83; 95% Cl: 0.47,1.19; P < .01). 4 studies showed that the shiver incidence of the experimental group was significantly lower than the control group (OR:0.29; 95% Cl: 0.19,0.46; P < .01). Conclusion: The results of this study suggest that active body temperature protection may be effective on intraoperative bleeding in elderly patients undergoing arthroplasty, as evidenced by blood loss, number of blood transfusions, intraoperative temperature, postoperative temperature, shiver incidence, length of hospital stay.

19.
Chem Biodivers ; 20(11): e202300999, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37933979

RESUMO

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-ß-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs.


Assuntos
Dendrobium , NF-kappa B , NF-kappa B/metabolismo , Macrófagos Alveolares/metabolismo , Transdução de Sinais , Anti-Inflamatórios/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-37971447

RESUMO

Objective: To explore the value of Doppler ultrasound combined with the serum pregnancy associated plasma protein A (PAPP-A) in the diagnosis and pathology of placenta accreta. Methods: For the method of retrospective study, the data of 250 pregnant women with cesarean section delivery in our hospital from February 2020 to February 2021 were analyzed, and the prenatal examination of pregnant women was performed by Doppler ultrasound and the serum PAPP-A level was determined by serology detection. They were divided into the placenta accreta group (n=152) and non-placenta accreta group (n=98) according to the pathological results after delivery to compare the imaging data and the serum PAPP-A levels in the two groups. The receiver operating characteristic curve (ROC curve) was drawn with the pathological results as the gold standard. Results: The serum PAPP-A level in the placenta accreta group was overtly lower than that in the non-placenta accreta group (698.65±9.65 vs 910.57±9.65, t = 169.52, P < .001). In the placenta accreta group, there were 126 cases (82.89%) with irregular gyrate liquid dark area formed in the placenta of pregnant women, 78 cases (51.32%) with partial or all disappearance of posterior placenta space, 22 cases (14.74%) with the attenuation or disappearance of myometrium in the placental attachment, and 20 cases (13.16%) with abnormal placental thickening. The sensitivity, specificity, positive predictive value and negative predictive value of the Doppler ultrasound combined with serum diagnosis of PAPP-A were 86.84%, 79.59%, 86.84% and 79.59%, respectively. ROC analysis showed that the area under the curve (AUC) of Doppler ultrasound combined with serum diagnosis of PAPP-A was 0.835, with the asymptotic Sig.b < .001 and an asymptotic 95% confidence interval (CI) of 0.780-0.891. Conclusion: Doppler ultrasound could analyze the pathological manifestations of placenta accreta, and serum PAPP-A could be combined to improve the detection rate of placenta accreta, with a certain clinical application value.

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