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1.
Artigo em Inglês | MEDLINE | ID: mdl-38419560

RESUMO

BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.

2.
Mol Ther Nucleic Acids ; 34: 102063, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38028203

RESUMO

Ferroptosis is an iron-catalyzed form of regulated cell death that results from the accumulation of lipid peroxidation products and reactive oxygen species to a lethal content. However, the transcriptional regulation of ferroptosis is not well understood. Sorafenib, a standard drug for hepatocellular carcinoma (HCC), induces ferroptosis in HCC cells. In this study, we conducted a CRISPR-Cas9 library screening targeting epigenetic factors and identified coactivator-associated arginine methyltransferase 1 (CARM1) as a critical inhibitor of ferroptosis. CARM1 depletion intensified Sorafenib-induced ferroptosis, resulting in decreased cell viability, reduced cellular glutathione level, increased lipid peroxidation, and altered mitochondrial crista structure. Additionally, we investigated a CARM1 inhibitor (CARM1i) as a potential ferroptosis inducer. Combining the CARM1i with Sorafenib enhanced the induction of ferroptosis. Notably, both CARM1 knockdown and CARM1i showed cooperative effects with Sorafenib in inhibiting HCC growth in mice. The underlying mechanism involves CARM1-catalyzed H3R26me2a on the promoter of glutathione peroxidase 4, leading to its transcriptional activation and subsequent ferroptosis inhibition. Furthermore, Sorafenib treatment induced the transcription of CARM1 through the MDM2-p53 axis. In summary, our findings establish CARM1 as a critical ferroptosis inhibitor and highlight the potential of CARM1is as novel ferroptosis inducers, providing promising therapeutic strategies for HCC treatment.

3.
Am J Sports Med ; 51(14): 3790-3801, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37975494

RESUMO

BACKGROUND: Fibroblast activation protein (FAP) has shown high expression in inflammatory responses and fibrosis. HYPOTHESIS: We speculated that FAP could serve as a diagnostic and monitoring target in the tendon healing process. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 72 Sprague-Dawley rats were randomly divided into a tendon crush group and a half-partial tendon laceration group. Four rats in each group were injected with radiotracers weekly for 4 weeks after surgery, with aluminum fluoride-labeled 1,4,7-triazacyclononane-N,N',N″-triacetic acid-conjugated FAP inhibitor (Al18F-NODA-FAPI-04) administered on the first day of each week and 18F-fludeoxyglucose (18F-FDG) on the next day. Small animal positron emission tomography (PET) imaging was performed, and tendon tissue was collected for pathology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis each week after surgery. RESULTS: One week after surgery, both radiotracers showed signal concentration at the lesion site, which was the highest radioactive uptake observed during 4 weeks postoperatively, consistent with the severity of the lesion. Consistent trends were observed for inflammatory cytokines during qRT-PCR analysis. Additionally, Al18F-NODA-FAPI-04 PET exhibited a more precise lesion pattern, attributed to its high specificity for naive fibroblasts when referring to histological findings. Over time, the uptake of both radiotracers at the injury site gradually decreased, with 18F-FDG experiencing a more rapid decrease than Al18F-NODA-FAPI-04. In the fourth week after surgery, the maximum standardized uptake values of Al18F-NODA-FAPI-04 in the injured lesion almost reverted to the baseline levels, indicating a substantial decrease in naive fibroblasts and inflammatory cells and a reduction in inflammation and fibrosis, especially compared with the first week. Corresponding trends were also revealed in pathological and qRT-PCR results. CONCLUSION: Our findings suggest that inflammation is a prominent feature during the early stage of tendon injury. Al18F-NODA-FAPI-04 PET allows accurate localization and provides detailed morphological imaging, enabling continuous monitoring of the healing progress and assessment of injury severity.


Assuntos
Tendão do Calcâneo , Traumatismos do Tornozelo , Traumatismos dos Tendões , Ratos , Animais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tendão do Calcâneo/diagnóstico por imagem , Fluordesoxiglucose F18 , Ratos Sprague-Dawley , Tomografia por Emissão de Pósitrons , Traumatismos dos Tendões/diagnóstico por imagem , Fibroblastos , Fibrose , Inflamação
4.
Zhongguo Zhong Yao Za Zhi ; 48(16): 4536-4544, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37802880

RESUMO

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Controle de Qualidade , Indústria Farmacêutica , Tecnologia Farmacêutica/métodos , Preparações Farmacêuticas
5.
Front Neurol ; 14: 1250808, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780718

RESUMO

Peripheral nerve injuries (PNIs) can be caused by various factors, ranging from penetrating injury to compression, stretch and ischemia, and can result in a range of clinical manifestations. Therapeutic interventions can vary depending on the severity, site, and cause of the injury. Imaging plays a crucial role in the precise orientation and planning of surgical interventions, as well as in monitoring the progression of the injury and evaluating treatment outcomes. PNIs can be categorized based on severity into neurapraxia, axonotmesis, and neurotmesis. While PNIs are more common in upper limbs, the localization of the injured site can be challenging. Currently, a variety of imaging modalities including ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) and positron emission tomography (PET) have been applied in detection and diagnosis of PNIs, and the imaging efficiency and accuracy many vary based on the nature of injuries and severity. This article provides an overview of the causes, severity, and clinical manifestations of PNIs and highlights the role of imaging in their management.

6.
Am J Chin Med ; 51(8): 2157-2173, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37865871

RESUMO

Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos, has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15[Formula: see text]mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86[Formula: see text]) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206[Formula: see text]) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF-[Formula: see text]B pathway activation via inhibiting NF-[Formula: see text]B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF-[Formula: see text]B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.


Assuntos
Traumatismos Cardíacos , Choque Hemorrágico , Triterpenos , Humanos , Masculino , Ratos , Animais , NF-kappa B/metabolismo , Choque Hemorrágico/complicações , Choque Hemorrágico/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Macrófagos/metabolismo , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Interleucina-1/metabolismo , Traumatismos Cardíacos/metabolismo
7.
J Hand Ther ; 36(4): 786-795, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37598094

RESUMO

BACKGROUND: Primary flexor tendon repairs of lacerations in zone II of the hand are fraught with problems. Traditionally, exercise (active and passive), orthoses, and physical agents are common interventions for the rehabilitation of patients experiencing these issues. One area of focus in this field is how to safely utilize tension to lengthen gliding distance following zone II injury. Finding effective solutions in this area is a key priority for improving patient outcomes and quality of life. PURPOSE: To identify the optimal immobilization position that meets safety standards for tension and is the most efficient, and consequently, to validate our clinical effectiveness. STUDY DESIGN: A cross-sectional study was adopted for the first part of the research (Research 1). A prospective, parallel, 2-group, randomized trial was conducted with concealed allocation and single blinding in the second part of the research (Research 2). METHODS: A total of 60 healthy adults were recruited to select the best-fit protective immobilization position in Research 1, which was confirmed by tendon tension (via Young's modulus) and excursion (via gliding distance). We then randomly assigned 45 patients after zone II flexor tendon repair into two groups in Research 2 to compare functional outcomes. The control group underwent the conventional modified Duran protocol with early passive motion, while the experimental group received the protocol (optimized by Research 1) with early active motion. Ultrasonography was used to measure the tension and excursion of the flexor tendons. The outcomes measured at 16 weeks post-repair included total active motion, strength, the Disabilities of the Arm, Shoulder and Hand, and Strickland scores. RESULTS: Three participants were unable to participate in Research 2 due to medical issues and poor attendance. The investigation found that the safe tendon threshold was 345.09 ± 87.74 kPa for partial active digital motion among the 60 participants. The optimal immobilization position requires the wrist to be neutral with a flexion angle of 30° at the metacarpophalangeal joint. The grip strengths (p = 0.012), ratio of grip strength (p = 0.015), the Disabilities of the Arm, Shoulder and Hand (p = 0.036), and total active motion (p = 0.023) differed significantly between the two groups. CONCLUSIONS: Protective immobilization of the wrist in a neutral flexion position and with the metacarpophalangeal joint flexed at 30° can secure the repaired flexor tendon safely and efficiently. The effects of an early active motion protocol may improve the grip strength and upper limb mobility of individuals after zone II flexor tendon repair. CLINICAL TRIAL REGISTRATION: ChiCTR2000030592.


Assuntos
Traumatismos dos Dedos , Traumatismos dos Tendões , Adulto , Humanos , Traumatismos dos Tendões/reabilitação , Estudos Transversais , Estudos Prospectivos , Qualidade de Vida , Tendões/cirurgia , Traumatismos dos Dedos/cirurgia , Ultrassonografia , Amplitude de Movimento Articular
8.
Photodiagnosis Photodyn Ther ; 44: 103760, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37634605

RESUMO

Timely identification and complete removal of oral squamous cell carcinoma (OSCC) through surgery is crucial for effective treatment. However, current diagnostic methods that rely on physical abnormalities are not very informative and practical in clinical settings, leading to the late detection of oral cancer. Furthermore, no dependable intraoperative tools available for assessing surgical margins in real-time. Fluorescence imaging allows the visualization of biological processes occurring in the early stages of cancer, and as a result, small tumors can be detected at an early stage. Fluorescence imaging can effectively aid in assessing excised edges during surgery for OSCC as it possesses high sensitivity and spatial resolution. This review focuses on tongue cancer as a representation of OSCC and delves into various fluorescence techniques that can aid in early diagnosis and surgical guidance. The review also discusses the potential clinical applications of these techniques in the future.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Fotoquimioterapia , Humanos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Imagem Óptica/métodos , Imagem Molecular
9.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3440-3447, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-37474981

RESUMO

With the rapid development of computer technology, numerical simulation has gradually become an important method to study drying process and improve drying equipment. Using computer to simulate the drying process of traditional Chinese medicine(TCM) is characterized by intuitiveness, scientificity, and low cost, which serves as an auxiliary means for technical innovation in TCM drying. This paper summarizes the theories of different drying methods and the research status of numerical simulation in drying, introduces the modeling methods and software of numerical simulation, and expounds the significance of numerical simulation modeling in shortening the research and development cycle, improving drying equipment, and optimizing drying parameters. However, the current numerical simulation method for drying process has problems, such as low accuracy, lack of quantitative indicators for the control of simulation results on the process, and insufficient in-depth research on the mechanism of drug quality changes. Furthermore, this paper put forward the application prospect of numerical simulation in TCM drying, providing reference for the further study of numerical simulation in this field.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Dessecação
11.
Front Oncol ; 13: 1126721, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37284201

RESUMO

Background: The cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers. Methods: In this study, [18F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo. Results: Radiolabeling of ADH-1 with [18F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of >97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [18F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor. Conclusion: [18F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.

12.
Intern Emerg Med ; 18(6): 1673-1679, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37284931

RESUMO

The lack of a highly sensitive method to evaluate paraquat (PQ)-induced pulmonary fibrosis and predict disease progression remains an unresolved clinic issue. Fibroblast activation protein (FAP) may play an important role in the pathogenesis of PQ-induced pulmonary fibrosis. We aimed to evaluate the role of FAP in the PQ-induced pulmonary fibrosis and the utility of fibroblast activation protein inhibitor (FAPI) for positron emission tomography (PET) imaging in PQ-induced pulmonary fibrosis. In our study, two cases of PQ poisoning were presented and FAPI PET/CT was performed as a novel imaging technique. The uptake of FAPI increased in both cases of PQ poisoning. Animal experiments were then performed to validate the findings in the patients. Physiological FAPI lung uptake was higher in mice of the PQ group than in the control group. The results of histological analysis and Western blot were consistent with the findings of PET/CT imaging. The pulmonary fibrosis animal model was developed by intragastric gavage of PQ. PET/CT imaging was performed after injection of FAPI. Lung tissues of mice were collected for fibrosis assessment after imaging. Immunohistochemistry for FAP, histology and Western blot for collagen were performed to further validate the imaging findings. In conclusion, FAPI was involved in the pathogenesis of fibrosis induced by PQ, and PET/CT with FAPI could detect lung fibrogenesis, making it a promising tool to assess early disease activity and predict disease progression.


Assuntos
Fibrose Pulmonar , Camundongos , Humanos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/metabolismo , Paraquat , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Progressão da Doença
13.
Elife ; 122023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36951548

RESUMO

As a ubiquitous picophytoplankton in the ocean and an early-branching green alga, Ostreococcus tauri is a model prasinophyte species for studying the functional evolution of the light-harvesting systems in photosynthesis. Here, we report the structure and function of the O. tauri photosystem I (PSI) supercomplex in low light conditions, where it expands its photon-absorbing capacity by assembling with the light-harvesting complexes I (LHCI) and a prasinophyte-specific light-harvesting complex (Lhcp). The architecture of the supercomplex exhibits hybrid features of the plant-type and the green algal-type PSI supercomplexes, consisting of a PSI core, an Lhca1-Lhca4-Lhca2-Lhca3 belt attached on one side and an Lhca5-Lhca6 heterodimer associated on the other side between PsaG and PsaH. Interestingly, nine Lhcp subunits, including one Lhcp1 monomer with a phosphorylated amino-terminal threonine and eight Lhcp2 monomers, oligomerize into three trimers and associate with PSI on the third side between Lhca6 and PsaK. The Lhcp1 phosphorylation and the light-harvesting capacity of PSI were subjected to reversible photoacclimation, suggesting that the formation of OtPSI-LHCI-Lhcp supercomplex is likely due to a phosphorylation-dependent mechanism induced by changes in light intensity. Notably, this supercomplex did not exhibit far-red peaks in the 77 K fluorescence spectra, which is possibly due to the weak coupling of the chlorophyll a603-a609 pair in OtLhca1-4.


Assuntos
Clorófitas , Complexo de Proteína do Fotossistema I , Complexo de Proteína do Fotossistema I/química , Complexos de Proteínas Captadores de Luz/química , Complexos de Proteínas Captadores de Luz/metabolismo , Clorofila , Fotossíntese , Clorófitas/metabolismo
14.
Cancers (Basel) ; 15(3)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36765712

RESUMO

BACKGROUND: N-cadherin is considered a characteristic protein of EMT and has been found to be closely related to tumor resistance. In this study, a novel molecular imaging probe, 99mTc-HYNIC-ADH-1, was developed, and its diagnostic value in monitoring drug resistance in NSCLC was preliminarily investigated. METHODS: ADH-1 was labeled indirectly with 99mTc. Radiochemical purity and stability, partition coefficients and pharmacokinetics were evaluated. Additionally, the fluorescent probe of ADH-1 was synthesized to study tumor uptake in cells level and in vivo. Biodistribution analysis and small animal SPECT/CT were performed in PC9GR and PC9 tumor-bearing mice. RESULTS: 99mTc-HYNIC-ADH-1 was highly stable (radiochemical purity ≥ 98% in PBS and serum after 24 h). A cell binding study and fluorescence imaging showed that the uptake was significantly higher in PC9GR cells (gefitinib-resistant) than in PC9 cells (nonresistant) (p < 0.05). Biodistribution analysis showed rapid blood clearance and significant uptake in the kidney and resistant tumor. Small animal SPECT/CT studies showed that uptake in PC9GR tumors (T/NT = 7.73 ± 0.54) was significantly higher than that in PC9 tumors (T/NT = 3.66 ± 0.78) at 1 h (p = 0.002). CONCLUSIONS: The 99mTc-HYNIC-ADH-1 molecular probe has a short synthesis time, high labeling rate, high radiochemical purity and good stability, does not require purification, is characterized by rapid blood clearance and is mainly excreted through the urinary system. 99mTc-HYNIC-ADH-1 is considered a promising probe for monitoring drug resistance in NSCLC.

15.
Cancers (Basel) ; 15(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36831535

RESUMO

Cancer represents a major cause of death worldwide and is characterized by the uncontrolled proliferation of abnormal cells that escape immune regulation. It is now understood that cancer-associated fibroblasts (CAFs), which express specific fibroblast activation protein (FAP), are critical participants in tumor development and metastasis. Researchers have developed various FAP-targeted probes for imaging of different tumors from antibodies to boronic acid-based inhibitor molecules and determined that quinoline-based FAP inhibitors (FAPIs) are the most appropriate candidate as the radiopharmaceutical for FAPI PET/CT imaging. When applied clinically, FAPI PET/CT yielded satisfactory results. Over the past few years, the utility and effectiveness of tumor detection and staging of FAPI PET/CT have been compared with FDG PET/CT in various aspects, including standardized uptake values (SUVs), rate of absorbance and clearance. This review summarizes the development and clinical application of FAPI PET/CT, emphasizing the diagnosis and management of various tumor types and the future prospects of FAPI imaging.

16.
Nature ; 615(7951): 349-357, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36702157

RESUMO

Chloroplasts rely on the translocon complexes in the outer and inner envelope membranes (the TOC and TIC complexes, respectively) to import thousands of different nuclear-encoded proteins from the cytosol1-4. Although previous studies indicated that the TOC and TIC complexes may assemble into larger supercomplexes5-7, the overall architectures of the TOC-TIC supercomplexes and the mechanism of preprotein translocation are unclear. Here we report the cryo-electron microscopy structure of the TOC-TIC supercomplex from Chlamydomonas reinhardtii. The major subunits of the TOC complex (Toc75, Toc90 and Toc34) and TIC complex (Tic214, Tic20, Tic100 and Tic56), three chloroplast translocon-associated proteins (Ctap3, Ctap4 and Ctap5) and three newly identified small inner-membrane proteins (Simp1-3) have been located in the supercomplex. As the largest protein, Tic214 traverses the inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins. An inositol hexaphosphate molecule is located at the Tic214-Toc90 interface and stabilizes their assembly. Four lipid molecules are located within or above an inner-membrane funnel formed by Tic214, Tic20, Simp1 and Ctap5. Multiple potential pathways found in the TOC-TIC supercomplex may support translocation of different substrate preproteins into chloroplasts.


Assuntos
Chlamydomonas reinhardtii , Cloroplastos , Microscopia Crioeletrônica , Complexos Multiproteicos , Transporte Proteico , Cloroplastos/química , Cloroplastos/metabolismo , Cloroplastos/ultraestrutura , Chlamydomonas reinhardtii/química , Chlamydomonas reinhardtii/ultraestrutura , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Complexos Multiproteicos/ultraestrutura , Ácido Fítico/metabolismo , Estabilidade Proteica , Especificidade por Substrato
17.
Chinese Journal of School Health ; (12): 1665-1669, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-998874

RESUMO

Objective@#To explore the role of mobile phone addiction and anxiety symptoms in the relationship between childhood psychological abuse and depressive symptoms among college students, in order to provide a basis for mental health promotion.@*Methods@#From February to May 2023, a stratified random sampling method was used to select 1 799 freshmen to juniors from a university in Wuhu City, Anhui Province. The questionnaire survey was conducted using the 2-item Patient Health Questionnaire (PHQ-2), Child Psychological Maltreatment Scale (CPMS), Mobile Phone Addiction Tendency Scale (MPATS), 2-item General Anxiety Disorder (GAD-2). Correlations among each variable were analyzed, and the chain mediating effect of mobile phone addiction and anxiety symptoms was explored.@*Results@#The detection rate of depressive symptoms among college students was 9.7%, and the positive detection rate of childhood psychological abuse was 28.6%. Depressive symptoms were positively correlated with childhood psychological abuse, mobile phone addiction and anxiety symptoms ( r =0.28, 0.32, 0.27, P <0.01). Childhood psychological abuse was positively correlated with mobile phone addiction and anxiety symptoms ( r =0.29, 0.71, P <0.01). Mobile phone addiction and anxiety symptoms were positively correlated ( r =0.30, P <0.01). Childhood psychological abuse could effectively predict depressiove symptoms, mobile phone addiction and anxiety symptoms ( β =0.08, 0.06, 0.66, P <0.01). Mobile phone addiction and anxiety symptoms had a chain mediating effect between childhood psychological abuse and depression symptoms, with a total indirect mediating effect (effect=25.27%, P <0.05), accounting for 72.44% of the total effect.@*Conclusions@#Mobile phone addiction and anxiety symptoms play a chain mediating role between childhood psychological abuse and depressive symptoms. Focusing on childhood psychological abuse, mobile phone addiction and anxiety among college students are beneficial for depression symptoms prevention.

18.
Front Cardiovasc Med ; 9: 994826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386321

RESUMO

In this study, the diagnostic value of microRNAs (miRNAs) for hypertension (HTN) with left ventricular hypertrophy (LVH) were evaluated by meta-analysis. A correlation study of the diagnostic value of miRNAs in HTN with LVH was conducted using a computer search of the China Knowledge Network (CNKI), Wanfang, VIP, China Biomedical Literature Database (CBM), PubMed, Web of Science, and Embase. Studies from the time of database creation to May 2022 were evaluated. The quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool in RevMan 5.3 was used to evaluate the quality of the literature, and Meta-Disc 1.4 and Stata 16.0, were used to calculate the combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic advantage ratio (DOR), and their 95% confidence intervals. Subject working characteristic curves were plotted and the area under the curve (AUC) was calculated using Stata 16.0. Seven publications and 8 studies were included. miRNA diagnoses of HTN with LVH had SENcombined = 0.84, SPEcombined = 0.80, PLRcombined = 4.2, NLRcombined = 0.20, DORcombined = 21, and AUCcombined = 0.89. Subgroup analysis showed that the sensitivity of plasma miRNA for the diagnosis of HTN with LVH was 0.85, which was higher than that of serum which was 0.83. The specificity of serum miRNA for the diagnosis of HTN with LVH was 0.82, which was higher than that of plasma which was 0.78, and the diagnostic accuracy of miRNA in serum DOR was 23, which was higher than that of plasma DOR which was 20. In the diagnosis of HTN with LVH, miRNA has high sensitivity and specificity and is a better biological marker. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, CRD42022346686.

20.
ACS Appl Mater Interfaces ; 14(38): 42887-42903, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36094079

RESUMO

Acetaminophen (APAP)-induced liver injury (AILI) is a common liver disease in clinical practice. Only one clinically approved drug, N-acetylcysteine (NAC), for the treatment of AILI is available in clinics, but novel treatment strategies are still needed due to the complicated pathological changes of AILI and the side effects of NAC. Here, we found that astaxanthin (ASX) can prevent AILI through the Nrf2/HO-1 pathway. After treatment with ASX, there was a positive activation of the Nrf2/HO-1 pathway in AILI models both in vivo and in vitro accompanied by enhanced autophagy and reduced ferroptosis. In APAP-challenged L02 liver cells, ASX reduced autophagy and enhanced apoptosis of the cells. Furthermore, we developed ASX-loaded hollow mesoporous silica nanoparticles (HMSN@ASX) to improve the aqueous solubility of ASX and targeted delivery of ASX to the liver and then significantly improve the therapeutic effects. Taken together, we found that ASX can protect against AILI by activating the Nrf2/HO-1 pathway, which mainly affects oxidative stress, autophagy, and ferroptosis processes, and the HMSN@ASX nanosystem can target the liver to enhance the treatment efficiency of AILI.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Ferroptose , Neuropatia Hereditária Motora e Sensorial , Acetaminofen/metabolismo , Acetilcisteína , Autofagia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Heme Oxigenase-1/metabolismo , Neuropatia Hereditária Motora e Sensorial/tratamento farmacológico , Neuropatia Hereditária Motora e Sensorial/metabolismo , Neuropatia Hereditária Motora e Sensorial/patologia , Humanos , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Dióxido de Silício/farmacologia , Xantofilas
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