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Saline-alkali stress is a widely distributed abiotic stress that severely limits plant growth. γ-Aminobutyric acid (GABA) accumulates rapidly in plants under saline-alkali stress, but the underlying molecular mechanisms and associated regulatory networks remain unclear. Here, we report a MYB-like protein, I-box binding factor (SlMYBI), which positively regulates saline-alkali tolerance through induced GABA accumulation by directly modulating the glutamic acid decarboxylase (GAD) gene SlGAD1 in tomato (Solanum lycopersicum L.). Overexpression of SlGAD1 increased GABA levels and decreased reactive oxygen species (ROS) accumulation under saline-alkali stress, while silencing of SlGAD1 further suggested that SlGAD1 plays an active role in GABA synthesis and saline-alkali tolerance of tomato. In addition, we found that SlMYBI activates SlGAD1 transcription. Both overexpression of SlMYBI and editing of SlMYBI using CRISPR/Cas9 showed that SlMYBI regulates GABA synthesis by modulating SlGAD1 expression. Furthermore, the interaction of SlNF-YC1 with SlMYBI enhanced the transcriptional activity of SlMYBI on SlGAD1 to further improve saline-alkali tolerance in tomato. Interestingly, we found that ethylene signaling was involved in the GABA response to saline-alkali stress by RNA-seq analysis of SlGAD1-overexpressing lines. This study elucidates the involvement of SlMYBI in GABA synthesis regulation. Specifically, the SlMYBI-SlNF-YC1 module is involved in GABA accumulation in response to saline-alkali stress.
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Although formononetin has a considerable biological activity, its therapeutic use is limited by its low solubility. Formononetin was dissolved in ethanol, methanol, N, N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO) in this investigation, the antisolvent precipitation procedure with the assistance of an external ultrasonic probe was used to manufacture the formononetin nano-particles. The ideal parameters for response surface BBD optimization are as follows: feed volume flow rate of 6 mL/min; ultrasonic power of 860 W; and liquid-liquid ratio of 1:12.5. The formononetin nano-particles have a smaller particle diameter than raw sample; the lowest size can be as small as (329 ± 1.99) nm, which is 45 times smaller than raw. An in vitro digestion test using a solution that simulated intestinal solution revealed that the release rate of the nano-particle was 1.75 times than that of the raw formononetin. The formononetin nano-particles generated by the aforementioned four solvents have the following order of diameter: ethanol > methanol > DMF > DMSO. This study provided a technical reference for the functional food components in deep processing.
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Background: Desmopressin acetate (DDAVP) and behavioral interventions (BI) are cornerstone treatments for nocturnal enuresis (NE), a common pediatric urinary disorder. Despite the growing body of clinical studies on massage therapy for NE, comprehensive evaluations comparing the effectiveness of Tuina with DDAVP or BI are scarce. This study aims to explore the efficacy of Tuina in the management of NE. Methods: A systematic search of international databases was conducted using keywords pertinent to Tuina and NE. The inclusion criteria were limited to randomized controlled trials (RCTs) that evaluated NE treatments utilizing Tuina against DDAVP or BI. This meta-analysis included nine RCTs, comprising a total of 685 children, to assess both complete and partial response rates. Results: Tuina, used as a combination therapy, showed enhanced clinical efficacy and improved long-term outcomes relative to the control group. The therapeutic efficacy of Tuina was not directly associated with the number of acupoints used. Instead, employing between 11 and 20 acupoints appeared to have the most significant effect. Conclusion: The findings of this meta-analysis support the potential of Tuina as an adjunct therapy to enhance the sustained clinical efficacy of traditional treatments for NE. However, Tuina cannot completely replace DDAVP or BI in the management of NE. While this study illuminates some aspects of the effective acupoint combinations, further research is crucial to fully understand how Tuina acupoints contribute to the treatment of NE in children. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=442644, identifier CRD42023442644.
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Background: Pressure injuries are present in all healthcare environments and not only pose a significant health risk to individuals but also impose a heavy economic burden on society and families. Nurses, as the primary caregivers responsible for the prevention and management of pressure injuries, have knowledge that directly determines the incidence of pressure injuries. Aim: To understand the current status of nurses' knowledge of pressure injuries in Shaanxi Province and the factors influencing it. Design: A cross-sectional survey. Methods: In April - May 2022, 16,599 nurses from hospitals at all levels in Shaanxi Province were selected as survey subjects by convenience sampling method. They were surveyed using the general information questionnaire and the Pieper-Zulkowski pressure injury Knowledge Questionnaire through the Questionnaire Star platform. Results: 16,599 nurses had a pressure injury knowledge score of (44.32±10.11). Wound description and pressure ulcer staging dimensions were less than 60% correct. Comparison of pressure injury knowledge scores of nursing staff with different genders, hospital levels, titles, education, whether they were specialized nurses in wound stoma when they last attended a lecture on pressure ulcers, when they last read literature or books on pressure ulcers, and whether they ever looked for information about pressure ulcers on the Internet showed that the differences were statistically significant (P < 0.05), which were the influencing factors of the knowledge scores of the nursing staff in Shaanxi Province. Conclusion: Clinical nurses' awareness of stress-related injuries still needs to be improved, and nursing administrators can improve the quality of pressure-related injury care by increasing nursing staff's awareness through continuing education, tiered training, and other measures.
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Cold stress significantly limits the yield and quality of tomato. Deciphering the key genes related to cold tolerance is important for selecting and breeding superior cold-tolerant varieties. γ-aminobutyric acid (GABA) responds to various types of stress by rapidly accumulating in plant. In this study, glutamic acid decarboxylase (GAD2) was a positive regulator to enhance cold stress tolerance of tomato. Overexpression of SlGAD2 decreased the extent of cytoplasmic membrane damage and increased the endogenous GABA content, antioxidant enzyme activities, and reactive oxygen species (ROS) scavenging capacity in response to cold stress, whereas Slgad2 mutant plants showed the opposite trend. In addition, SlGAD2 induced anthocyanin biosynthesis in response to cold stress by increasing the content of endogenous GABA. Further study revealed that SlGAD2 expression was negatively regulated by the transcription factor SlTHM27. However, the transcript levels of SlTHM27 were repressed under cold stress. Antioxidant enzyme activities, SlGAD2 transcript levels, GABA and anthocyanin contents were significantly increased in Slthm27 mutant plants. Further, our study demonstrated that SlTHM27 decreases SlGAD2-promoted cold resistance in tomato by repressing SlGAD2 transcription. Overall, our results showed that the SlTHM27-SlGAD2 model regulates the cold tolerance in tomato by regulating GABA and anthocyanin.
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The occurrence of rheumatoid arthritis (RA) is highly correlated with progressive and irreversible damage of articular cartilage and continuous inflammatory response. Here, inspired by the unique structure of synovial lipid-hyaluronic acid (HA) complex, we developed supramolecular HA-nanomedicine hydrogels for RA treatment by mediating macrophage-synovial fibroblast cross-talk through locally sustained release of celastrol (CEL). Molecular dynamics simulation confirmed that HA conjugated with hydrophobic segments could interspersed into the CEL-loaded [poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone] (PECT) nanoparticles to form the supramolecular nanomedicine hydrogel HA-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-un-decanone)/PECT@CEL (HP@CEL), enabling fast hydrogel formation after injection and providing a 3-dimensional environment similar with synovial region. More importantly, the controlled release of CEL from HP@CEL inhibited the macrophage polarization toward the proinflammatory M1 phenotype and further suppressed the proliferation of synovial fibroblasts by regulating the Toll-like receptor pathway. In collagen-induced arthritis model in mice, HP@CEL hydrogel treatment substantial attenuated clinical symptoms and bone erosion and improved the extracellular matrix deposition and bone regeneration in ankle joint. Altogether, such a bioinspired injectable polymer-nanomedicine hydrogel represents an effective and promising strategy for suppressing RA progression through augmenting the cross-talk of macrophages and synovial fibroblast for regulation of chronic inflammation.
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Objectives: To investigate the effect of different designs of movable parts and prosthetic materials on the stress distribution of supporting tissues in mandibular free end dentition defects using three-dimensional finite element analysis of digital Roach attachments. Material and methods: A 3D model of a patient with Kennedy class I mandibular edentulous conditions was generated, and twelve prosthesis models were applied, combining two designs of removable parts and six types of CAD/CAM restorative materials with different elastic modulus (conventional zirconia, ultra-translucent zirconia, Polyetheretherketone (PEEK), Lithium disilicate, Nanoceramic resin, and resin composite (Paradigm MZ100, 3 M ESPE)). The stress distribution of abutment periodontal ligament, edentulousmucosa, and junction of attachment were analyzed using finite element analysis. Results: The stress value of the buccal neck of the periodontal ligament and the maximum compressive stress of the distal periodontal ligament of the design with clasp arms were higher than those without clasp arms, while the stress on the junction of attachment and the displacement of the mucosa in the edentulous area were smaller. Restorative materials with high elastic modulus, such as conventional zirconia and ultra-translucent zirconia, are recommended to be used as the fixed part of Roach attachment. Conclusion: CAD/CAM Roach attachments with clasp arms are recommended for the protection of mucosal soft tissue. Restorative materials with high elastic modulus, such as conventional zirconia and ultra-translucent zirconia, are recommended as the fixed part of Roach attachment for patients with free end defect of mandibular dentition. Clinical significance: This study provides references for the design with clasp arms and the selection of clinical fixed-movable prosthetic materials. Clinicians should consider the design of attachments and selection of appropriate manufacturing materials carefully to avoid negative impacts on patients' periodontal support tissues.
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Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long-term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l-lactic acid)-gelatin-A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein-derived peptides (A5G81) to the surface of polydioxanone and poly (l-lactic acid) fibers. The polymer microfiber-biomacromolecule-peptide frame with biophysical and biochemical cues could orchestrate the biomaterial-host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti-inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell-biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell-material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.
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Gelatina , Dispositivo Oclusor Septal , Animales , Porcinos , Gelatina/química , Polidioxanona , Células Endoteliales , Polímeros , Materiales Biocompatibles , Ácido Láctico , PéptidosRESUMEN
INTRODUCTION: Cervical squamous cell carcinoma (CESC) is the most common gynecological malignancy worldwide. Although the cancer susceptibility 18 (CASC18) gene was involved in the regulation of cancer biology, its specific role in CESC is not well characterized. METHODS: CASC18-related axis was predicted by bioinformatic analyses, and the competing endogenous RNA (ceRNA) interaction was further validated using quantitative real-time PCR, western blotting, RNA pulldown, and luciferase reporter assays. Transwell and wound healing assays were performed to verify the effect of CASC18 on SiHa and HeLa cell motility. RESULTS: We found that CASC18 was upregulated in CESC tissues. Moreover, interference with CASC18 attenuated NUAK1-mediated epithelial-mesenchymal transition (EMT) and thus suppressed cancer cell motility. Furthermore, the effects of CASC18 knockdown on CESC cells were partly rescued by transfection with the miR-5586-5p inhibitor. Additionally, our findings indicated that CASC18 acts as a ceRNA to enhance NUAK1 expression by sponging miR-5586-5p. CONCLUSION: Our study showed a novel CASC18/miR-5586-5p/NUAK1 ceRNA axis that could regulate cell invasion and migration by modulating EMT in CESC. These findings suggest that CASC18 may potentially serve as a novel therapeutic target in CESC treatment.
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Carcinoma de Células Escamosas , MicroARNs , Neoplasias del Cuello Uterino , Femenino , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias del Cuello Uterino/genética , Células HeLa , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Invasividad Neoplásica/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Proteínas Represoras/metabolismoRESUMEN
Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.
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The primary cause of injury and death in the elderly has been reflected in fall the elderly, so the application of reasonable and effective prevention strategies has great significance in reducing the risk of fall in the elderly. The research progress of virtual reality technology applied in preventing fall in the elderly at home and abroad over the years was systematically reviewed in this study. The mechanism of the technology in preventing fall in the elderly was mainly elaborated from five aspects of improving balance ability, gait disturbance, cognitive impairment, muscle strength and the fear psychology of falling. The purpose of this thesis is to broaden the research ideas of medical personnel on the prevention of fall of the elderly, provide more effective clinical practice plans, reduce the occurrence of fall, and guarantee the safety of the elderly.
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Marcha , Realidad Virtual , Anciano , Humanos , Fuerza Muscular , TecnologíaRESUMEN
Tetanus toxin (TeNT) and botulinum neurotoxins (BoNTs) are neuroprotein toxins, with the latter being the most toxic known protein. They are structurally similar and contain three functional domains: an N-terminal catalytic domain (light chain), an internal heavy-chain translocation domain (HN domain), and a C-terminal heavy chain receptor binding domain (Hc domain or RBD). In this study, fusion functional domain molecules consisting of the TeNT RBD (THc) and the BoNT/A RBD (AHc) (i.e., THc-Linker-AHc and AHc-Linker-THc) were designed, prepared, and identified. The interaction of each Hc domain and the ganglioside receptor (GT1b) or the receptor synaptic vesicle glycoprotein 2 (SV2) was explored in vitro. Their immune response characteristics and protective efficacy were investigated in animal models. The recombinant THc-linker-AHc and AHc-linker-THc proteins with the binding activity had the correct size and structure, thus representing novel subunit vaccines. THc-linker-AHc and AHc-linker-THc induced high levels of specific neutralizing antibodies, and showed strong immune protective efficacy against both toxins. The high antibody titers against the two novel fusion domain molecules and against individual THc and AHc suggested that the THc and AHc domains, as antigens in the fusion functional domain molecules, do not interact with each other and retain their full key epitopes responsible for inducing neutralizing antibodies. Thus, the recombinant THc-linker-AHc and AHc-linker-THc molecules are strong and effective bivalent biotoxin vaccines, protecting against two biotoxins simultaneously. Our experimental design will be valuable to develop recombinant double-RBD fusion molecules as potent bivalent subunit vaccines against bio-toxins. KEY POINTS: ⢠Double-RBD fusion molecules from two toxins had the correct structure and activity. ⢠THc-linker-AHc and AHc-linker-THc efficiently protected against both biotoxins. ⢠Such bivalent biotoxin vaccines based on the RBD are a valuable experimental design.
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Toxinas Botulínicas Tipo A , Toxina Tetánica , Animales , Toxina Tetánica/genética , Toxina Tetánica/metabolismo , Toxinas Botulínicas Tipo A/genética , Toxinas Botulínicas Tipo A/metabolismo , Unión Proteica , Anticuerpos Neutralizantes , Vacunas de Subunidad/genéticaRESUMEN
Postoperative abdominal adhesion is a very common and serious complication, resulting in pain, intestinal obstruction and heavy economic burden. Post-injury inflammation that could activate the coagulation cascade and deposition of fibrin is a major cause of adhesion. Many physical barrier membranes are used to prevent abdominal adhesion, but their efficiency is limited due to the lack of anti-inflammatory activity. Here, an electrospinning membrane composed of poly(lactic-co-glycolic acid) (PLGA) providing support and mechanical strength and chondroitin sulfate (CS) conferring anti-inflammation activity is fabricated for preventing abdominal adhesion after injury. The PLGA/CS membrane shows a highly dense fiber network structure with improved hydrophilicity and good cytocompatibility. Importantly, the PLGA/CS membrane with a mass ratio of CS at 20% provides superior anti-adhesion efficiency over a native PLGA membrane and commercial poly(D, L-lactide) (PDLLA) film in abdominal adhesion trauma rat models. The mechanism is that the PLGA/CS membrane could alleviate the local inflammatory response as indicated by the promoted percentage of anti-inflammatory M2-type macrophages and decreased expression of pro-inflammatory factors, such as IL-1ß, TNF-α and IL-6, resulting in the suppression of the coagulation system and the activation of the fibrinolytic system. Furthermore, the deposition of fibrin at the abdominal wall was inhibited, and the damaged abdominal tissue was repaired with the treatment of the PLGA/CS membrane. Collectively, the PLGA/CS electrospinning membrane is a promising drug-/cytokine-free anti-inflammatory barrier for post-surgery abdominal adhesion prevention and a bioactive composite for tissue regeneration.
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Sulfatos de Condroitina , Glicoles , Humanos , Ratas , Animales , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Adherencias Tisulares/prevención & control , Adherencias Tisulares/metabolismo , Antiinflamatorios/farmacologíaRESUMEN
Background: Progression of disease within 24 months (POD24) is a risk factor for poor survival in follicular lymphoma (FL), and there is currently no optimal prognostic model to accurately predict patients with early disease progression. How to combine traditional prognostic models with new indicators to establish a new prediction system, to predict the early progression of FL patients more accurately is a future research direction. Methods: This study retrospectively analyzed patients with newly diagnosed FL patients in Shanxi Provincial Cancer Hospital from January 2015 to December 2020. Data from patients undergoing immunohistochemical detection (IHC) were analyzed using χ2 test and multivariate Logistic regression. Also, we built a nomogram model based on the results of LASSO regression analysis of POD24, which was validated in both the training set and validation set, and additional external validation was performed using a dataset (n = 74) from another center, Tianjin Cancer Hospital. Results: The multivariate Logistic regression results suggest that high-risk PRIMA-PI group, Ki-67 high expression represent risk factors for POD24 (P<0.05). Next, PRIMA-PI and Ki67 were combined to build a new model, namely, PRIMA-PIC to reclassify high and low-risk groups. The result showed that the new clinical prediction model constructed by PRIMA-PI with ki67 has a high sensitivity to the prediction of POD24. Compared to PRIMA-PI, PRIMA-PIC also has better discrimination in predicting patient's progression-free survival (PFS) and overall survival (OS). In addition, we built nomogram models based on the results of LASSO regression (histological grading, NK cell percentage, PRIMA-PIC risk group) in the training set, which were validated using internal validation set and external validation set, we found that C-index and calibration curve showed good performance. Conclusion: As such, the new predictive model-based nomogram established by PRIMA-PI and Ki67 could well predict the risk of POD24 in FL patients, which boasts clinical practical value.
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Background: In 2017, the Chinese government launched a pilot project in palliative care, in which Shanghai was a pioneer. Nurses play a key role in palliative care services as they are the main providers improving the quality of services for patients and their families. However, little is known about practices and influencing factors in the field of palliative care from a nursing perspective in China. This is an original empirical study that has meticulously analyzed the interrelationship and intensity between practices and other factors among nurses in the initial stage of palliative care in primary healthcare institutions in Shanghai, China. Methods: A descriptive-correlational study design was used to sample 2,829 eligible palliative care nurses by purposive sampling survey in 225 healthcare institutions in Shanghai, China. Descriptive analyses were performed using IBM SPSS 24.0 software. Structural equation modeling was applied to analyze the data by AMOS 20.0. Data were collected using the well-designed Knowledge, Attitudes, and Practices of Hospice Care (KAPHC) scale. Results: The final model showed a good model fit. Self-efficacy directly influenced practices (ß = 0.506, P < 0.01) and indirectly influenced practices (ß = 0.028, P < 0.01) through intention. Subjective norm directly influenced practices (ß = 0.082, P < 0.01) and indirectly influenced practices (ß = 0.030, P < 0.01) through intention. Intention (ß = 0.152, P < 0.01) and knowledge (ß = 0.068, P < 0.01) directly influenced practices. Perceived susceptibility (ß = -0.027, P < 0.01), perceived benefits (ß = -0.017, P < 0.01), and perceived barriers (ß = -0.014, P < 0.01) indirectly influenced practices through intention. Conclusion: This study provided evidence of the associations of knowledge, perceived susceptibility, benefits, barriers, subjective norm, self-efficacy, intention, and practices among nurses concerning palliative care and interventions improving their actual work practices. Our findings revealed that self-efficacy, intention, and subjective norms greatly influenced practices. It is imperative to take interventions that focus precisely on self-efficacy, intention, and subjective norms to improve nurses' practices.
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Enfermeras y Enfermeros , Cuidados Paliativos , Humanos , Proyectos Piloto , China , ActitudRESUMEN
The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage-endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.
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Hidrogeles , Infarto del Miocardio , Porcinos , Animales , Glicopéptidos , Infarto del Miocardio/metabolismo , Matriz Extracelular/metabolismo , InflamaciónRESUMEN
BACKGROUND: Baphicacanthis Cusiae Rhizoma et Radix, commonly known as Nan-Ban-Lan-Gen (NBLG), is an essential traditional Chinese medicine that possesses diverse bioactivities, particularly noteworthy for its antiviral properties. Although NBLG has been listed in the Chinese Pharmacopoeia as an independent Chinese medicine, the establishment of a comprehensive quality standard for NBLG remains elusive. The absence of assay for marker compound in its quality standards has led to the lack of corresponding quality control measures for NBLG-containing preparations, and its discrimination from adulterant species in the market which thereby can significantly impact the efficacy and safety of NBLG-containing products. METHODS: Ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole-time-of-flight mass spectrometry (Q-TOF-MS) was employed for comprehensive profiling of the chemical constituents of NBLG, the stem of Baphicacanthus cusia (Nees) Bremek (NBLJ), and the roots of Isatis indigotica Fort. (Bei-Ban-Lan-Gen, BBLG). Additionally, multivariate analysis was conducted to compare the chemical components of NBLG with those of NBLJ and BBLG. Furthermore, we established an optimized and validated HPLC method to obtain the fingerprint of NBLG and quantify the content of 2-benzoxazolinone and acteoside in the samples. RESULTS: A total of 73 compounds belonging to six classes were assigned in NBLG, with alkaloids being the most abundant and diverse species. High compositional similarities with significant differences in content were observed between NBLG and NBLJ. Moreover, the chemical profile of BBLG markedly differed from that of NBLG. An informative high performance liquid chromatography (HPLC) fingerprint of NBLG comprising seven characteristic peaks that can be used for quality assessment was established. Notably, we propose a quality control standard for NBLG, stipulating that the limit of content in dry weight for both 2-benzoxazolinone and acteoside should not be less than 0.010%. CONCLUSION: This study provides the most comprehensive chemical information to date on NBLG, offering valuable insights into its authentication and quality control. Our findings highlight the importance of comprehensive chemical profiling to differentiate potential substitutions and adulterations of herbal medicines, particularly when the original source is scarce or unavailable. These results can aid in the development of quality control measures for NBLG-containing preparations, ensuring their safety and efficacy.
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Anti-angiogenic therapies targeting inhibition of vascular endothelial growth factor (VEGF) pathway show clinical benefit in hypervascular hepatocellular carcinoma (HCC) tumors. However, HCC expresses massive pro-angiogenic factors in the tumor microenvironment (TME) in response to anti-angiogenic therapy, recruiting tumor-associated macrophages (TAMs), leading to revascularization and tumor progression. To regulate cell types in TME and promote the therapeutic efficiency of anti-angiogenic therapy, a supramolecular hydrogel drug delivery system (PLDX-PMI) co-assembled by anti-angiogenic nanomedicines (PCN-Len nanoparticles (NPs)) and oxidized dextran (DX), and loaded with TAMs-reprogramming polyTLR7/8a nanoregulators (p(Man-IMDQ) NRs) is developed for orthotopic liver cancer therapy. PCN-Len NPs target tyrosine kinases of vascular endothelial cells and blocked VEGFR signaling pathway. p(Man-IMDQ) NRs repolarize pro-angiogenic M2-type TAMs into anti-angiogenic M1-type TAMs via mannose-binding receptors, reducing the secretion of VEGF, which further compromised the migration and proliferation of vascular endothelial cells. On highly malignant orthotopic liver cancer Hepa1-6 model, it is found that a single administration of the hydrogel formulation significantly decreases tumor microvessel density, promotes tumor vascular network maturation, and reduces M2-subtype TAMs, thereby effectively inhibiting tumor progression. Collectively, findings in this work highlight the great significance of TAMs reprogramming in enhancing anti-angiogenesis treatment for orthotopic HCC, and provides an advanced hydrogel delivery system-based synergistic approach for tumor therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Macrófagos Asociados a Tumores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales/metabolismo , Hidrogeles/uso terapéutico , Nanomedicina , Polímeros/uso terapéutico , Microambiente TumoralRESUMEN
Purpose: Acupuncture can improve symptoms of autism spectrum disorder (ASD), but the potential mechanisms remain undefined. So, we aimed to explore the behavioral improvement of autism rat model after acupuncture and to describe the potential molecular mechanism underlying these changes. Patients and Methods: Wistar rats were intraperitoneally injected with VPA 12.5 days after conception, and their offspring were considered as good models of autism. Experimental rats were divided into three groups (wild-type (WT), n = 10; VPA, n = 10; and VPA_acupuncture, n = 10). VPA_acupuncture group rat received 4 weeks of acupuncture treatment (Shéntíng (GV24), and Bilateral Benshén (GB13)) on the 23rd day after birth. All rats were subjected to behavioral tests, including social interaction, open field, and Morris water maze tests. Afterwards, hippocampal tissues (left side) were removed and subjected to RNA sequencing (RNA-seq) analysis; ELISA was also used to detect the associated serotonin levels in the hippocampus. Results: Behavioral tests showed that acupuncture treatment improved spontaneous activity, aberrant social interaction, and alleviated impaired learning and memory in the VPA-induced rat model. Differentially expressed genes (DGEs) analysis showed 142 significantly differentially expressed genes between WT and VPA groups, and 282 between VPA and VPA_acupuncture rats. Htr2c and Htr1a, 5-HT receptor genes, were up-regulated in the VPA group compared with WT group. Additionally, Tph1, a rate-limiting enzyme gene of 5-HT synthesis, was up-regulated after acupuncture. These genes were confirmed to have the same trend of expression obtained by RT-qPCR and RNA seq. Furthermore, the concentration of serotonin in the hippocampus in the VPA group was significantly lower than the WT and VPA_acupuncture groups. Conclusion: Acupuncture improved abnormal behavioral symptoms in the VPA-induced rat model. Further experiments showed that the improvement of the serotonin system may be one of the main regulatory mechanisms of acupuncture for treating ASD.
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BACKGROUND: Hospice and palliative care nursing (HPCN) in China is mainly available at public primary care institutions, where nursing homes (NHs) are rarely involved. Nursing assistants (NAs) play an essential role in HPCN multidisciplinary teams, but little is known about their attitudes towards HPCN and related factors. METHODS: A cross-sectional study was designed to evaluate NAs' attitudes towards HPCN with an indigenised scale in Shanghai. A total of 165 formal NAs were recruited from 3 urban and 2 suburban NHs between October 2021 and January 2022. The questionnaire was composed of four parts: demographic characteristics, attitudes (20 items with four sub-concepts), knowledge (nine items), and training needs (nine items). Descriptive statistics, independent samples t-test, one-way ANOVA, Pearson's correlation, and multiple linear regression were performed to analyse NAs' attitudes, influencing factors, and their correlations. RESULTS: A total of 156 questionnaires were valid. The mean score of attitudes was 72.44 ± 9.56 (range:55-99), with a mean item score of 3.6 ± 0.5 (range:1-5). The highest score rate was "perception of the benefits for the life quality promotion" (81.23%), and the lowest score rate was "perception of the threats from the worsening conditions of advanced patients" (59.92%). NAs' attitudes towards HPCN were positively correlated with their knowledge score (r = 0.46, P < 0.01) and training needs (r = 0.33, P < 0.01). Marital status (ß = 0.185), previous training experience (ß = 0.201), location of NHs (ß = 0.193), knowledge (ß = 0.294), and training needs (ß = 0.157) for HPCN constituted significant predictors of attitudes (P < 0.05), which explained 30.8% of the overall variance. CONCLUSION: NAs' attitudes towards HPCN were moderate, but their knowledge should be improved. Targeted training is highly recommended to improve the participation of positive and enabled NAs and to promote high-quality universal coverage of HPCN in NHs.