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1.
Sports Health ; : 19417381241264493, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39108063

RESUMO

BACKGROUND: Quadriceps and hamstring strength deficits are related to the increased risk of reinjury after anterior cruciate ligament reconstruction (ACLR). HYPOTHESIS: Knee angle-specific quadriceps and hamstring strength differences would be observed in patients with ACLR 6 and 12 months after surgery. STUDY DESIGN: Case-series. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 23 postprimary unilateral ACLR patients followed-up at 6 and 12 months postoperatively and 25 controls were included. Isokinetic knee extension and flexion strength were evaluated at 60 deg/s from 20° to 90°. Statistical parametric mapping were performed to explore the angle-specific strength and the limb symmetry index (LSI). RESULTS: At 6 months postoperatively, the reconstructed leg demonstrated lower knee extension and flexion strength than the contralateral (20°-77°, 24°-90°) (P < 0.01) and control legs (22°-90°, 40°-82°) (P < 0.01). From 6 months to 12 months, knee extension (60°-90°) and flexion (20°-79°) strength improved in the reconstructed leg (P < 0.05), while LSI remained unchanged (P > 0.02). At 12 months, knee extension strength differences persisted in the reconstructed leg compared with the contralateral (20°-81°) and controls (25°-63°) (P < 0.01). ACLR patients had lower LSI of knee extension strength at 6 (20°-59°) and 12 (24°-57°) months postoperatively than the controls (P < 0.02). CONCLUSION: The reconstructed leg exhibited differences in knee extension strength compared with the contralateral and control legs. Although bilateral knee extension strength increased from 6 to 12 months postoperatively, LSI did not show improvement during this period. CLINICAL RELEVANCE: Quadriceps restoration was observed only in knee flexion angles greater than 60° compared with controls. Future studies should investigate whether knee extension strength, especially in lower flexion angles, can be enhanced through rehabilitation programs. Furthermore, assessing the impact of this improvement on long-term outcomes and reinjury risk in ACLR patients is warranted.

2.
Int Immunopharmacol ; 141: 112918, 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39159558

RESUMO

Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient's life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1ß) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.

3.
FASEB J ; 38(15): e23857, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39114953

RESUMO

Atherosclerotic plaque formation is largely attributed to the impaired efferocytosis, which is known to be associated with the pathologic upregulation of cluster of differentiation 47 (CD47), a key antiphagocytic molecule. By gene expression omnibus (GEO) datasets analysis, we identified that four miRNAs are aberrantly downregulated in atherosclerosis, coronary artery disease, and obesity. Of them, hsa-miR-299-3p (miR-299-3p) was predicted to target the 3'UTR of human CD47 mRNA by bioinformatics analysis. Further, we demonstrated that miR-299-3p negatively regulates CD47 expression by binding to the target sequence "CCCACAU" in the 3'UTR of CD47 mRNA through luciferase reporter assay and site-directed mutagenesis. Additionally, we found that miR-299-3p was downregulated by ~32% in foam cells in response to oxidized low-density lipoprotein (ox-LDL) stimulation, thus upregulating CD47 and contributing to the impaired efferocytosis. Whereas, restoration of miR-299-3p reversed the ox-LDL-induced upregulation of CD47, thereby facilitating efferocytosis. In high-fat diet (HFD) fed ApoE-/- mice, we discovered that miR-299-3p was downregulated thus leading to upregulation of CD47 in abdominal aorta. Conversely, miR-299-3p restoration potently suppressed HFD-induced upregulation of CD47 and promoted phagocytosis of foam cells by macrophages in atherosclerotic plaques, thereby reducing necrotic core, increasing plaque stability, and mitigating atherosclerosis. Conclusively, we identify miR-299-3p as a negative regulator of CD47, and reveal a molecular mechanism whereby the ox-LDL-induced downregulation of miR-299-3p leads to the upregulation of CD47 in foam cells thus contributing to the impaired efferocytosis in atherosclerosis, and propose miR-299-3p can potentially serve as an inhibitor of CD47 to promote efferocytosis and ameliorate atherosclerosis.


Assuntos
Aterosclerose , Antígeno CD47 , Eferocitose , MicroRNAs , Animais , Humanos , Camundongos , Regiões 3' não Traduzidas , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Antígeno CD47/metabolismo , Antígeno CD47/genética , Dieta Hiperlipídica/efeitos adversos , Células Espumosas/metabolismo , Células Espumosas/patologia , Lipoproteínas LDL/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo
4.
Sci Total Environ ; 946: 174375, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38960175

RESUMO

Groundwater contamination by nitrate and sulfate in mining areas is a significant challenge. Consequently, the inputs sources of these contaminants and their evolution have received considerable attention, with the knowledge gained critical for improved management of water quality. This study integrated data on multiple stable isotopes and water chemistry data and a Bayesian isotope mixing model to investigate the relative contributions of inputs sources of sulfate and nitrate sources to bodies of water in a karst mining area in southwest China. The outcomes indicated that hydrochemical component in the water bodies of the study area is mainly derived from the dissolution of silicate rocks, carbonate rocks and sulfate minerals as well as the oxidation of sulfides. The human and agricultural wastewater, soil nitrogen, and fertilizers were the predominant inputs sources of nitrate to the mine water environment; the predominant inputs sources of sulfide were mineral oxidation, evaporite dissolution, atmospheric deposition, and sewage. Groundwater is mainly recharged from atmospheric precipitation, and surface water is closely hydraulically connected to groundwater. Nitrogen and oxygen isotope composition and water chemistry indicative of nitrification dominate the nitrogen cycle in the study area. The oxidation of pyrite and bacterial sulfate reduction (SRB) had no significant impact on the stable isotopes of groundwater. The results of this study demonstrate the inputs of different sources to nitrate and sulfate in karst mines and associated transformation processes. The results of this study can assist in the conservation of groundwater quality in mining areas and can act as a reference for future related studies.

5.
Int J Pharm ; 660: 124334, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38871135

RESUMO

Tranexamic acid (TXA) is an anti-fibrinolysis agent widely used in postoperative blood loss management. As a highly water-soluble drug, TXA is suffering from rapid clearance from the action site, therefore, large amount of drug is required when administered either by intravenously or topically. In this study, a TXA preparation with prolonged action site residence was designed using the nano-micro strategy. TXA nanoparticles were dispersed in oil by emulsification followed by lyophilization to give a solid-in-oil suspension, which was used as the oil phase for the preparation of TXA-loaded solid-in-oil-in-water (TXA@S/O/W) system. The particle size of TXA in oil was 207.4 ± 13.50 nm, and the particle size of TXA@S/O/W was 40.5 µm. The emulsion-in-gel system (TXA@S/O/G) was prepared by dispersing TXA@S/O/W in water solution of PLGA-b-PEG-b-PLGA (PPP). And its gelling temperature was determined to be 26.6 ℃ by a rheometer. Sustained drug release was achieved by TXA@S/O/G with 72.85 ± 7.52 % of TXA released at 120 h. Formulation retention at the joint cavity was studied by live imaging, and the fluorescent signals dropped gradually during one week. Drug escape from the injection site via drainage and absorption was investigated by a self-made device and plasma TXA concentration determination, respectively. TXA@S/O/G showed the least drug drainage during test, while more than 70 % of drug was drained in TXA@S/O/W group and TXA solution group. Besides, low yet steady plasma TXA concentration (less than 400 ng/mL) was found after injecting TXA@S/O/G into rat knees at a dosage of 2.5 mg/kg, which was much lower than those of TXA dissolved in PPP gel or TXA solution. In conclusion, sustained drug release as well as prolonged action site retention were simultaneously achieved by the designed TXA@S/O/G system. More importantly, due to the steady plasma concentration, this strategy could be further applied to other highly water-soluble drugs with needs on sustained plasma exposure.


Assuntos
Antifibrinolíticos , Emulsões , Nanopartículas , Ácido Tranexâmico , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/farmacocinética , Ácido Tranexâmico/química , Animais , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/química , Antifibrinolíticos/farmacocinética , Masculino , Nanopartículas/química , Polietilenoglicóis/química , Tamanho da Partícula , Ratos Sprague-Dawley , Géis , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Óleos/química , Ratos , Poliésteres/química , Portadores de Fármacos/química , Poliglactina 910
6.
Appl Opt ; 63(15): 4219-4225, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38856516

RESUMO

We propose a method using electromagnetically induced transparency (EIT) to measure the frequency offset of the laser relative to a cavity's resonance frequency, thereby reducing the laser detuning when preparing Rydberg atoms. Laser reflection by the vapor cell enables observation of two EIT peaks corresponding to the co-propagating and counter-propagating beams, and the peaks' position is related to laser detuning, allowing us to estimate the frequency offset of the probe and coupling lasers. The method reduces the measurement uncertainty compared to directly observing saturated absorption spectroscopy (SAS) and EIT, making it suitable for applications that require strict control over laser detuning.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38836729

RESUMO

Objective: This study aimed to explore the therapeutic effects of the combined use of omalizumab with conventional anti-allergy treatment for IgE-mediated allergic diseases and to provide new treatment options for the clinical management of IgE-mediated allergic diseases. Methods: Patients with IgE-mediated allergic diseases who visited the Allergy Department of the First Hospital of Hebei Medical University between June 2020 and June 2022 were randomly divided into two groups: the conventional anti-allergy treatment group (control) and the experimental group receiving conventional treatment combined with omalizumab. The treatment lasted for 24 weeks, with patient follow-up and evaluation of treatment effects for seasonal allergic rhinitis, allergic asthma, and urticaria. Results: The evaluation of treatment effects for seasonal allergic rhinitis, urticaria, and allergic rhinitis showed that the experimental group had significantly better outcomes than the control group. Conclusion: The combined use of omalizumab with conventional anti-allergy treatment was effective in treating IgE-mediated seasonal allergic rhinitis, urticaria, and allergic asthma, providing a new therapeutic option for the clinical management of IgE-mediated allergic diseases.

8.
J Chromatogr A ; 1730: 465099, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38901298

RESUMO

A miniaturized microchip-based absorbance detector was developed for portable high-performance liquid chromatography (HPLC) to test glycated hemoglobin (HbA1c). The microchip integrating a Z-shaped cell, two collimating micro-lenses and two ink-filled optical slits is small in size (30 mm × 15 mm × 7 mm). The Z-shaped cell has a cross-sectional size of 500 µm × 500 µm and a physical optical path length of 2 mm. Two collimating micro-lenses were inserted in empty grooves on both sides of the cell, one micro-lens for collimating the initial light and the other for focusing the transmitted light. Optical slits on each end of the cell were used to block the stray light. Therefore, this detector indicated a low stray light level (0.011 %) and noise level (2.5 × 10-4 AU). This detector was applied for the commercial HPLC system to detect HbA1c level, and showed a low limit of detection (0.5 µg/mL) and excellent repeatability (≤ 2.03 %). The sensitivity was enhanced by 3.4 times when the optical path length was increased from 0.5 mm to 2 mm and the stray light was blocked by optical slits. The miniaturized microchip-based absorbance detector developed shows a great potential for application in portable and compact HPLC.


Assuntos
Desenho de Equipamento , Hemoglobinas Glicadas , Limite de Detecção , Cromatografia Líquida de Alta Pressão/métodos , Hemoglobinas Glicadas/análise , Humanos , Dispositivos Lab-On-A-Chip , Reprodutibilidade dos Testes
9.
J Foot Ankle Res ; 17(2): e12027, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38812103

RESUMO

PURPOSE: Abnormal lower limb movement patterns have been observed during walking in individuals with limited ankle dorsiflexion. The purpose of this study was to investigate the relationships of peak ankle dorsiflexion angle during the stance phase of walking with the lower extremity biomechanics at the corresponding moment and to determine a cutoff value of functional limited ankle dorsiflexion during walking. METHODS: Kinematic and kinetic data of 70 healthy participants were measured during walking. Spearman's correlation coefficients were calculated to establish the association between peak ankle dorsiflexion and angle and moment of ankle, knee, and hip, ground reaction force, and pelvic movement at peak ankle dorsiflexion. All variables significantly related to peak ankle dorsiflexion were extracted as a common factor by factor analysis. Maximally selected Wilcoxon statistic was used to perform a cutoff value analysis. RESULTS: Peak ankle dorsiflexion positively correlated with ankle plantar flexion moment (r = 0.432; p = 0.001), ankle external rotation moment (r = 0.251; p = 0.036), hip extension angle (r = 0.281; p = 0.018), hip flexion moment (r = 0.341; p = 0.004), pelvic ipsilateral rotation angle (r = 0.284; p = 0.017), and medial, anterior, and vertical ground reaction force (r = 0.324; p = 0.006, r = 0.543; p = 0.001, r = 0.322; p = 0.007), negatively correlated with knee external rotation angle (r = -0.394; p = 0.001) and hip adduction angle (r = -0.256; p = 0.032). The cutoff baseline value for all 70 participants was 9.03°. CONCLUSIONS: There is a correlation between the peak ankle dorsiflexion angle and the lower extremity biomechanics during walking. If the peak ankle dorsiflexion angle is less than 9.03°, the lower limb movement pattern will change significantly.


Assuntos
Articulação do Tornozelo , Extremidade Inferior , Amplitude de Movimento Articular , Caminhada , Humanos , Fenômenos Biomecânicos/fisiologia , Masculino , Feminino , Articulação do Tornozelo/fisiologia , Caminhada/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Extremidade Inferior/fisiologia , Adulto Jovem , Articulação do Quadril/fisiologia , Articulação do Joelho/fisiologia , Tornozelo/fisiologia
10.
Adv Healthc Mater ; 13(20): e2400400, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38769944

RESUMO

Vascular dementia (VaD) is the second most common form of dementia worldwide. Oxidative stress and neuroinflammation are important factors contributing to cognitive dysfunction in patients with VaD. The antioxidant and anti-inflammatory properties of hydrogen are increasingly being utilized in neurological disorders, but conventional hydrogen delivery has the disadvantage of inefficiency. Therefore, magnesium silicide nanosheets (MSNs) are used to release hydrogen in vivo in larger quantities and for longer periods of time to explore the appropriate dosage and regimen. In this study, it is observed that hydrogen improved learning and working memory in VaD rats in the Morris water maze and Y-maze, which elicits improved cognitive function. Nissl staining of neurons shows that hydrogen treatment significantly improves edema in neuronal cells. The expression and activation of reactive oxygen species (ROS), Thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-1ß in the hippocampus are measured via ELISA, Western blotting, real-time qPCR, and immunofluorescence. The results show that oxidative stress indicators and inflammasome-related factors are significantly decreased after 7dMSN treatment. Therefore, it is concluded that hydrogen can ameliorate neurological damage and cognitive dysfunction in VaD rats by inhibiting ROS/NLRP3/IL-1ß-related oxidative stress and inflammation.


Assuntos
Disfunção Cognitiva , Demência Vascular , Modelos Animais de Doenças , Hidrogênio , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Ratos Sprague-Dawley , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inflamassomos/metabolismo , Hidrogênio/farmacologia , Hidrogênio/química , Demência Vascular/tratamento farmacológico , Demência Vascular/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Ratos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos
11.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2023-2036, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812219

RESUMO

To evaluate the efficacy and safety of different Chinese patent medicines in the treatment of pelvic inflammatory disease(PID) using network Meta-analysis. The databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science were searched, and from the time of database construction to July 16, 2023, the randomized controlled trial(RCT) of Chinese patent medicines combined with antibiotics in the treatment of PID included in these databases was collected. The quality of the included literature was evaluated using the Cochrane risk of bias tool, and data was analyzed using RevMan 5.4 and Stata 16 software. Forty-six RCTs were finally included, including Kangfu Xiaoyan Suppositories, Fuke Qianjin Tablets/Capsules, Kangfuyan Capsules, Fuyanxiao Capsules, Huahong Tablets/Capsules, Fuyanshu Capsules, Fuyue Tablets, Jingangteng Capsules, and Fuyan Kangfu Capsules. Network Meta-analysis showed that,(1) in terms of clinical effective rate, the optimal intervention was Kangfu Xiaoyan Suppositories combined with antibiotics.(2) In terms of lowering hypersensitive C-reactive protein(hs-CRP), the optimal intervention was Huahong Tablets/Capsules combined with antibiotics.(3) In terms of lowering tumor necrosis factor-α(TNF-α), the optimal intervention was Fuyue Tablets combined with antibiotics.(4) In terms of lowering recurrence rate, the optimal intervention was Fuyanshu Capsules combined with antibiotics.(5) In terms of safety, the intervention with the least adverse reactions was Kangfuyan Capsules combined with antibiotics. The results show that Chinese patent medicines combined with antibiotics in the treatment of PID can improve the comprehensive efficacy, reduce the patient's hs-CRP and TNF-α, and have a low recurrence rate, as well as safe and reliable efficacy. In clinical treatment, Kangfu Xiaoyan Suppositories or Kangfuyan Capsules combined with antibiotics can be preferred. Due to the limitations of the sample size and the quality of the literature, more large-sample and high-quality studies are needed to validate the conclusions.


Assuntos
Antibacterianos , Medicamentos de Ervas Chinesas , Doença Inflamatória Pélvica , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Inflamatória Pélvica/tratamento farmacológico , Humanos , Feminino , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Quimioterapia Combinada , Medicamentos sem Prescrição
12.
Adv Rheumatol ; 64(1): 44, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816873

RESUMO

OBJECTIVES: Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, gut microbiota and its metabolites contribute to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear. In this study, we aimed to investigate whether gut microbiota and their metabolites alter the effects of high fat diet (HFD) on the severity of collagen-induced arthritis (CIA) in mice. METHODS: Briefly, mice were divided into normal group (N), CIA model group (C), HFD group (T), and HFD CIA group (CT). Hematoxylin and Eosin staining(HE) and Safranin O-fast green staining were conducted, and levels of blood lipid and inflammatory cytokines were measured. 16S rDNA sequencing technique and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics were performed to explore changes in the microbiota structure to further reveal the pathomechanism of HFD on CIA. RESULTS: HFD aggravated the severity of CIA in mice. The CT group had the highest proportion of microbial abundance of Blautia, Oscillibacter, Ruminiclostridium-9, and Lachnospiraceae UCG 006 at the genus level, but had a lower proportion of Alistipes. Additionally, the fecal metabolic phenotype of the combined CT group shows significant changes, with differential metabolites enriched in 9 metabolic pathways, including primary bile acid biosynthesis, arginine biosynthesis, sphingolipid metabolism, purine metabolism, linoleic acid metabolism, oxytocin signaling pathway, aminoacyl-tRNA biosynthesis, the pentose phosphate pathway, and sphingolipid signaling pathway. Correlation analysis revealed that some of the altered gut microbiota genera were strongly correlated with changes in fecal metabolites, total cholesterol (TC), triglyceride (TG), and inflammatory cytokine levels. CONCLUSIONS: This study shows that HFD may aggravate inflammatory reaction in CIA mice by altering the gut microbiota and metabolic pathways.


Assuntos
Artrite Experimental , Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Camundongos , Artrite Experimental/microbiologia , Artrite Experimental/metabolismo , Citocinas/metabolismo , Masculino , Índice de Gravidade de Doença , Obesidade/metabolismo , Obesidade/microbiologia , Modelos Animais de Doenças
13.
Front Neurol ; 15: 1327206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689877

RESUMO

Background: Bell's palsy is an acute peripheral facial neuropathy, which is one of the most common causes of facial palsy of lower motor neurons. Facial nerve swelling is commonly observed in Bell's palsy. Acupuncture therapy has been widely used in the treatment of Bell's palsy. However, whether acupuncture can be effectively used in the acute stage is still controversial. There are no clinical trials conducted previously to evaluate the effect of acupuncture on facial nerve edema in Bell's palsy patients. The study aims to evaluate the potential efficacy of different acupuncture modalities on Bell's palsy patients in the acute phase, its effect on facial nerve edema, and to preliminarily explore its possible mechanism. Methods and analysis: In this randomized, controlled trial, 165 Bell's palsy patients with unilateral onset within 3 days will be recruited and randomly assigned to either the electroacupuncture group (n = 33), the acupuncture group (n = 33), the sham acupuncture group (n = 33), the blank control group (n = 33), or the acupuncture control group (n = 33) in a 1:1:1:1:1 ratio. The participants will receive 4 weeks of treatment and 8 weeks of follow-up. The five groups of participants will receive the following treatments: A: Electroacupuncture + Medication (prednisone acetate tablets, mecobalamin tablets, and vitamin B1 tablets); B: Acupuncture + Medication; C: Sham Acupuncture + Medication; D: Medication only; and E: Acupuncture only. The primary outcome will be the effectiveness rate of different acupuncture modalities in improving facial nerve function after the intervention period. The secondary outcomes will be the recovery speed, the diameter of the facial nerve, the echo intensity and thickness of facial muscles, blood flow parameters of the facial artery, the serum inflammatory level, safety evaluation, and adverse events. Preliminary exploration of its mechanism of action occurs through inflammation and immune response. The difference between groups will be assessed using repeated measure analysis of covariance (ANCOVA) and trend chi-square. Discussion: The trial will evaluate the efficacy and facial nerve edema of acupuncture for Bell's palsy patients in the acute phase and preliminarily explore its possible mechanism. The results thus may provide evidence for clinical application. Clinical trial registration: https://www.chictr.org.cn/bin/project/edit?pid=133211, identifier ChiCTR2100050815.

14.
J Adv Res ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38768811

RESUMO

INTRODUCTION: The combination of a photosensitizer and indoleamine-2,3 dioxygenase (IDO) inhibitor provides a promising photoimmunotherapy (PIT) strategy for melanoma treatment. A dual drug delivery system offers a potential approach for optimizing the inhibitory effects of PIT on melanoma proliferation and metastasis. OBJECTIVE: To develop a dual drug delivery system based on PIT and to study its efficacy in inhibiting melanoma proliferation and metastasis. METHODS: We constructed a multifunctional nano-porphyrin material (P18-APBA-HA) using the photosensitizer-purpurin 18 (P18), hyaluronic acid (HA), and 4-(aminomethyl) phenylboronic acid (APBA). The resulting P18-APBA-HA was inserted into a phospholipid membrane and the IDO inhibitor epacadostat (EPA) was loaded into the internal phase to prepare a dual drug delivery system (Lip\EPA\P18-APBA-HA). Moreover, we also investigated its physicochemical properties, targeting, anti-tumor immunity, and anti-tumor proliferation and metastasis effects. RESULTS: The designed system utilized the pH sensitivity of borate ester to realize an enhanced-targeting strategy to facilitate the drug distribution in tumor lesions and efficient receptor-mediated cellular endocytosis. The intracellular release of EPA from Lip\EPA\P18-APBA-HA was triggered by thermal radiation, thereby inhibiting IDO activity in the tumor microenvironment, and promoting activation of the immune response. Intravenous administration of Lip\EPA\P18-APBA-HA effectively induced anti-tumor immunity by promoting dendritic cell maturation, cytotoxic T cell activation, and regulatory T cell suppression, and regulating cytokine secretion, to inhibit the proliferation of melanoma and lung metastasis. CONCLUSION: The proposed nano-drug delivery system holds promise as offers a promising strategy to enhance the inhibitory effects of the combination of EPA and P18 on melanoma proliferation and metastasis.

15.
Cancer Lett ; 590: 216847, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38583647

RESUMO

Tamoxifen (TAM) resistance presents a major clinical obstacle in the management of estrogen-sensitive breast cancer, highlighting the need to understand the underlying mechanisms and potential therapeutic approaches. We showed that dysregulated mitochondrial dynamics were involved in TAM resistance by protecting against mitochondrial apoptosis. The dysregulated mitochondrial dynamics were associated with increased mitochondrial fusion and decreased fission, thus preventing the release of mitochondrial cytochrome c to the cytoplasm following TAM treatment. Dynamin-related GTPase protein mitofusin 1 (MFN1), which promotes fusion, was upregulated in TAM-resistant cells, and high MFN1 expression indicated a poor prognosis in TAM-treated patients. Mitochondrial translocation of MFN1 and interaction between MFN1 and mitofusin 2 (MFN2) were enhanced to promote mitochondrial outer membrane fusion. The interaction of MFN1 and cristae-shaping protein optic atrophy 1 (OPA1) and OPA1 oligomerization were reduced due to augmented OPA1 proteolytic cleavage, and their apoptosis-promoting function was reduced due to cristae remodeling. Furthermore, the interaction of MFN1 and BAK were increased, which restrained BAK activation following TAM treatment. Knockdown or pharmacological inhibition of MFN1 blocked mitochondrial fusion, restored BAK oligomerization and cytochrome c release, and amplified activation of caspase-3/9, thus sensitizing resistant cells to apoptosis and facilitating the therapeutic effects of TAM both in vivo and in vitro. Conversely, overexpression of MFN1 alleviated TAM-induced mitochondrial apoptosis and promoted TAM resistance in sensitive cells. These results revealed that dysregulated mitochondrial dynamics contributes to the development of TAM resistance, suggesting that targeting MFN1-mediated mitochondrial fusion is a promising strategy to circumvent TAM resistance.


Assuntos
Apoptose , Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , GTP Fosfo-Hidrolases , Dinâmica Mitocondrial , Tamoxifeno , Humanos , Tamoxifeno/farmacologia , Dinâmica Mitocondrial/efeitos dos fármacos , Apoptose/efeitos dos fármacos , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Animais , Camundongos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Linhagem Celular Tumoral , Antineoplásicos Hormonais/farmacologia , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Células MCF-7 , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Am J Sports Med ; 52(6): 1428-1438, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38619003

RESUMO

BACKGROUND: Rotator cuff tears have been repaired using the transosseous method for decades. The direct suture (DS) technique has been widely used for rotator cuff tears; however, the retear rate is relatively high. Suture anchors are now used frequently for rotator cuff repair (RCR) in accordance with recent developments in materials. However, polyether ether ketone (PEEK) may still cause complications such as the formation of cysts and osteophytes. Some studies have developed the inlay suture (IS) technique for RCR. PURPOSE/HYPOTHESIS: To compare how 3 different surgical techniques-namely, the DS, IS, and PEEK suture anchor (PSA)-affect tendon-bone healing after RCR. We hypothesized that the IS technique would lead to better tendon-to-bone healing and that the repaired structure would be similar to the normal enthesis. STUDY DESIGN: Controlled laboratory study. METHODS: Acute infraspinatus tendon tears were created in 36 six-month-old male rabbits, which were divided into 3 groups based on the technique used for RCR: DS, IS, and PSA. Animals were euthanized at 6 and 12 weeks postoperatively and underwent a histological assessment and imaging. The expression of related proteins was demonstrated by immunohistochemistry and immunofluorescence staining. Mechanical properties were evaluated by biomechanical testing. RESULTS: At 12 weeks, regeneration of the enthesis was observed in the 3 groups. However, the DS group showed a lower type I collagen content than the PSA and IS groups, which was similar to the results for scleraxis. The DS group displayed a significantly inferior type II collagen expression and proteoglycan deposition after safranin O/fast green and sirius red staining. With regard to runt-related transcription factor 2 and alkaline phosphatase, the IS group showed upregulated expression levels compared with the other 2 groups. CONCLUSION: Compared with the DS technique, the PSA and IS techniques contributed to the improved maturation of tendons and fibrocartilage regeneration, while the IS technique particularly promoted osteogenesis at the enthesis. CLINICAL RELEVANCE: The IS and PSA techniques may be more beneficial for tendon-bone healing after RCR.


Assuntos
Benzofenonas , Cetonas , Polietilenoglicóis , Polímeros , Lesões do Manguito Rotador , Manguito Rotador , Âncoras de Sutura , Técnicas de Sutura , Animais , Coelhos , Masculino , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Cicatrização , Modelos Animais de Doenças
17.
Water Sci Technol ; 89(5): 1179-1194, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483492

RESUMO

The study investigated the denitrification effect of the iron autotrophic denitrification process for removing nitrite under anaerobic conditions, utilizing sponge iron as the electron donor. When the C/N ratio equaled 1, defined as the ratio of chemical oxygen demand to total nitrogen (TN), and the influent nitrite nitrogen (NO2--N) was at 80 mg/L, the average steady-state TN effluent concentration of this system was 41.94 mg/L during the 79-day experiment. The TN value exhibited a significant decrease compared to both the sponge iron system (68.69 mg/L) and the carbon source system (56.50 mg/L). Sponge iron is beneficial for providing an electron donor and ensuring an anaerobic system, fostering an environment that promotes microorganism growth while effectively inhibiting the conversion of nitrite to nitrate. In addition, carbon sources play a vital role in ensuring microorganism growth and reproduction, thereby aiding in TN removal. The optimal parameters based on the effectiveness of TN removal in the iron autotrophic denitrification system were determined to be s-Fe0 dosage of 30 g/L and C/N = 1.5. These results suggest that the iron autotrophic denitrification process, driven by sponge iron, can effectively remove nitrite under anaerobic conditions.


Assuntos
Desnitrificação , Nitritos , Anaerobiose , Reatores Biológicos , Carbono , Ferro , Nitrogênio
18.
Heliyon ; 10(4): e26430, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404844

RESUMO

Objective: To describe our experience of reducing anastomotic leakage, a problem that has not been properly solved. Methods: Starting in January 2020, we began implementing our integrated strategy (application of an esophageal diameter-approximated slender gastric tube, preservation of the fibrous tissue around the residual esophagus and thyroid inferior pole anastomosis) in consecutive patients undergoing esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube. Additionally, the blood supply at the site of the anastomosis was evaluated with a near-infrared fluorescence thoracoscope after the completion of esophagogastric anastomosis in the integrated strategy group. Results: Of 570 patients who were reviewed, 119 (20.9%) underwent the integrated strategy, and 451 (79.1%) underwent the conventional strategy. The rate of anastomotic leakage was 2.5% in the integrated strategy group and 10.2% in the conventional strategy group (p = 0.008). In the integrated strategy group, the site of most of the anastomotic blood supply was the residual esophagus dominant (82.4%), followed by the gastroesophageal dual-dominant (12.6%) and the gastric tube dominant (5.0%). The reconstruction route was more likely to be orthotopic in the integrated strategy group than in the conventional strategy group (89.9% vs. 38.6%, p = 0.004). Gastric dilation was identified in 3.4% of the patients in the integrated strategy group and in 21.1% in the conventional strategy group. Conclusions: Patients who underwent our proposed integrated strategy (Zhengzhou Strategy) during McKeown esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube had a strikingly lower rate of anastomotic leakage and a relatively lower rate of postoperative complications, such as gastric tube dilation and delayed gastric emptying.

19.
Diagn Pathol ; 19(1): 1, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173003

RESUMO

BACKGROUND: NRG1 fusion is a promising therapeutic target for various tumors but its prevalence is extremely low, and there are no standardized testing algorithms for genetic assessment. MOTHODS: In this study, we analyzed 3008 tumors using Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to screen for NRG1 translocation and p-HER3 expression. RESULTS: Our results demonstrated no cases with p-HER3 positivity through IHC. Nonetheless, 29 cases (0.96%) were identified positive for NRG1 translocation through FISH, with three different signal types. FISH-positive cases were subsequently subjected to next-generation sequencing (NGS) testing. However, only eight of these cases were confirmed with NRG1 fusion through NGS. Notably, we divided FISH into three types and FISH type C group was consistent with NGS results. All NGS NRG1 fusion tumors were adenocarcinomas, with a higher prevalence in females. Our findings indicate that although FISH has limitations in screening NRG1 gene rearrangements, NRG1 fusions can be reliably detected with signals exhibiting low copy numbers of the 5'-end of the gene and no fusion signals. CONCLUSION: Considering the high cost of NGS, FISH remains a useful method for screening NRG1 fusions in various types of tumors. This study provides valuable insights into the molecular mechanisms of NRG1 fusion and identifies potential treatment targets for patients suffering from this disease.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Feminino , Humanos , Neoplasias Pulmonares/patologia , Hibridização in Situ Fluorescente/métodos , Adenocarcinoma/patologia , Translocação Genética , Rearranjo Gênico , Proteínas de Fusão Oncogênica/genética , Neuregulina-1/genética , Neuregulina-1/uso terapêutico
20.
Angew Chem Int Ed Engl ; 63(16): e202401233, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38251909

RESUMO

Norcorrole Ni(II) complexes have recently received considerable attention because they are readily accessible antiaromatic molecules. Their high stability under ambient conditions and ease of synthesis have enabled the exploration of the intrinsic properties of antiaromatic molecules. Here, we report the synthesis and properties of meso-meso singly linked porphyrin-norcorrole hybrids and a triply linked porphyrin-norcorrole hybrid. The singly linked and triply linked porphyrin-norcorrole hybrids were fully characterized, including an X-ray structural analysis. Due to their orthogonal conformation, the singly linked hybrids maintain the individual electronic properties of their porphyrin and norcorrole subunits, while the triply linked hybrid shows a significantly smaller electrochemical HOMO-LUMO gap (0.45 eV) than that of Ni(II) dimesitylnorcorrole (1.08 eV). Furthermore, the triply linked hybrid exhibits singlet diradical characteristics, as confirmed by VT NMR, ESR, and SQUID experiments.

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