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PURPOSE: This study aims to define the computed tomography (CT) criteria that distinguish extra-gastrointestinal stromal tumors (eGISTs) from intra-abdominal fibromatosis (IAF). METHODS: Retrospective analysis was conducted on CT images obtained from 31 pathologically confirmed cases, including 17 cases of eGISTs and 14 of IAF. Various parameters [e.g., lesion location, contour characteristics, border delineation, enhancement patterns, presence of intralesional necrosis, vessels, air, fat, and hemorrhage, the long diameter (LD), LD/short diameter (SD) ratio, and volume (LD × SD × height diameter)] were meticulously evaluated. In addition, the degree of enhancement during arterial and portal venous phases and the lesion-to-aorta CT attenuation ratio during both phases were quantified. Statistical analysis was performed using Fisher's exact test, the Student's t-test, and the receiver operating characteristic curve to identify significant CT criteria. Sensitivity and specificity assessments were conducted for single and combined CT criteria. RESULTS: Significant differentiators between eGISTs and IAF include non-mesenteric localization, irregular contour, well-defined borders, heterogeneous enhancement, presence of intralesional necrosis and vessels, and absence of intralesional fat, with LD exceeding 9.6 cm, an LD/SD ratio >1.22, and volume surpassing 603.3 cm3 (P < 0.05). A combination of seven or more of these criteria yielded a specificity of 100%. CONCLUSION: Ten distinct CT criteria have been identified to distinguish eGISTs from IAF, notably encompassing non-mesenteric localization, irregular contour, well-defined borders, heterogeneous enhancement, presence of intralesional necrosis and vessels, absence of intralesional fat, LD >9.6 cm, an LD/SD ratio >1.22, and volume surpassing 603.3 cm3. CLINICAL SIGNIFICANCE: The current findings establish CT criteria to distinguish eGISTs from IAF in a clinical setting.
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Upon intravascular applications, i.e., cancer treatment, nanoparticles (NPs) are required to deliver through blood circulation, sustain serum protein interactions, before they penetrate the blood vessels and reach targeted sites for payload drug release. For a delivery process as such, it is elusive and difficult to comprehend the morphological change of NP surface and evaluate associated effects on its targeted delivery. Herein, we used silica NPs with different surface modifications to demonstrate the morphological impact of NPs during the application of the NP-blood protein interaction, vascular endothelial cell penetration, subsequent targeted delivery and photodynamic therapy efficacy, and pursue high drug-load NPs with surface designs. Compared to solid and mesoporous NPs, we found the spiky tubular NPs reserved the NPs' antifouling properties (or shedding of "protein corona"), promoted better endothelial penetration and less destruction in vitro and in vivo. Such effects could be attributed to their spiky surface structures, which can limit the NP-protein interaction area and promote the NP-protein steric hindrance. Further in molecular simulations, we determined that the spiky tubular morphological modification on NPs enhanced the interaction free energy and lowered the amino acids number and the subsequent frequency in contacting with VE-cadherin of vascular endothelia. As a result, the spiky tubular NPs demonstrated its advantages in mitigating damages to VE-cadherin stability and endothelial cell integrity. Exploiting such spiky tubular surface modification, we can improve the NP delivery efficiency and prohibit the leakiness of vascular endothelia, helping address challenges faced by tumor migration in nanomedicine applications for cancer therapy.
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Observational studies have suggested an association between metabolic syndrome (MetS) and hidradenitis suppurativa (HS), but whether this relationship is causal remains unclear. Elucidating the causal direction could provide insights into disease mechanisms and potential interventions. We performed bidirectional two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) of MetS and HS. For validation, we replicated the MetS analysis using data from an independent GWAS. We applied multiple MR methods, primarily inverse variance-weighted (IVW) regression, and conducted sensitivity analyses to assess heterogeneity and pleiotropy. The MR analysis demonstrated MetS causally increased HS risk (IVW odds ratio [OR], 1.428 [95% CI, 1.193-1.710]; p < 0.001), with consistent evidence from sensitivity analyses. However, HS did not appear to causally influence MetS risk (IVW OR, 1.008 [95% CI, 0.988-1.028]; p = 0.438). This study provides evidence that MetS causally increases the risk of developing HS. However, we found no evidence for a causal relationship in the reverse direction from HS to MetS. Further research is warranted to elucidate the mechanisms underlying the identified causal association between MetS and subsequent HS development.
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BACKGROUND: Multiple primary carcinomas (MPCs) are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual. Synchronous MPCs are rarer than solitary cancers or metachronous MPCs. Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases. CASE SUMMARY: A 64-year-old patient presented with dysphagia, without obvious cause. A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results. After multi-disciplinary consultations, combination chemotherapy (a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14) and esophageal cancer radiotherapy were initiated. Based on the results of genetic testing, we switched to a regimen of leucovorin + fluorouracil + oxaliplatin and cetuximab regimen for 8 cycles. Subsequently, capecitabine and bevacizumab were administered until the most recent follow-up, at which the tumor remained stable. CONCLUSION: Successful cetuximab chemotherapy treatment provides a reference for the non-operative and homogeneous treatment of different pathological types of synchronous MCPs.
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BACKGROUND: Acupuncture of the governor vessel and Yangming meridian are widely used in the treatment of acute ischemic stroke (AIS). However, the optimal meridian for acupuncture in the treatment of AIS remains uncertain. PURPOSE: This network meta-analysis study aimed to compare the clinical effectiveness of acupuncture at governor vessel and Yangming meridian in the treatment of AIS. METHODS: All relevant studies published in CNKI, WANFANG, VIP, Sinomed, Cochrane Library, Web of Science, Pub Med, and Embase before January 13, 2024 were systematically retrieved. The two researchers independently screened the studies and extracted the data. Cochrane ROB tool was used to evaluate the quality of the studies, and Stata 14.0 software was used to conduct a network meta-analysis of neurological deficit score, activities of daily living (ADL), clinical effective rate and Fugl-meyer motor function evaluation (FMA). RESULTS: A total of 401 studies were obtained, and 17 studies met the inclusion criteria. The surface under the cumulative ranking curve (SUCRA) values of the four outcome indexes were all ranked by "Governor vessel acupuncture + Conventional neurology treatment(GVAc+CT) > Yangming meridian acupuncture + Conventional neurology treatment(YMAc+CT) > Conventional neurology treatment (CT)". Compared to YMAc+CT and CT, GVAc+CT had the best effect in reducing the degree of neurological deficit score (SMD = -0.72, 95%CI = [-1.22,-0.21] and SMD = -1.07,95%CI = [-1.45,-0.69], respectively) and promoting the recovery of ADL((SMD = 0.59,95%CI = [0.31,0.88] and SMD = 0.96,95%CI = [0.70,1.21], respectively). Compared to CT, GVAc+CT also had a better clinical effective rate in the treatment of AIS (RR = 1.14,95%CI = [1.04,1.25]). CONCLUSIONS: Governor vessel acupuncture combined with conventional neurology treatment has the best effect in reducing the degree of neurological deficit score and promoting the recovery of ADL in AIS patientscompared to YMAc+CT and CT. Governor Vessel acupuncture is the most preferable acupoint scheme for clinical acupuncture treatment of AIS.
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Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Meridianos , Humanos , Terapia por Acupuntura/métodos , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/fisiopatología , Resultado del Tratamiento , Metaanálisis en Red , Actividades Cotidianas , Puntos de AcupunturaRESUMEN
The global outbreak of the COVID-19 pandemic has indisputably wreaked havoc on societies worldwide, compelling the scientific community to seek urgently needed therapeutic agents with low-cost and low-side effect profiles. Numerous approaches have been investigated in the quest to prevent or treat COVID-19, but many of them exhibit unwelcome side effects, such as dysfunctional viral immune responses and inflammation. Herein, we present the preparation of solid natural human pulmonary alveolar epithelial cell (ATII) membrane-coated PLGA NPs (PLGA NPs@ATII-M), which demonstrate remarkable affinity and competitiveness to neutralize the SARS-CoV-2 S1 protein-coated NPs (SCMMA NPs-S1), which are employed as a surrogate for coronavirus particles. In addition, we first considered the antifouling properties of these types of NPs, and we found that this membrane-coated NP formulation boasts excellent antifouling capabilities, which serve to protect their neutralization properties out of shielding by protein coronas in blood circulation. Moreover, this formulation is easily prepared and stored with a low-cost profile and exhibits good specificity, high targeting efficiency, and potentially side effect avoiding, thus making it a highly promising candidate for COVID-19 treatment.
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Incrustaciones Biológicas , COVID-19 , Nanopartículas , Humanos , SARS-CoV-2 , Pandemias/prevención & control , Tratamiento Farmacológico de COVID-19 , Nanopartículas/uso terapéutico , Membrana CelularRESUMEN
Nano-induced endothelial leakiness (NanoEL) can improve the ability of nanoparticles (NPs) to enter the tumor environment, nevertheless, it can inadvertently trigger adverse effects such as tumor metastasis. To overcome these concerns, it becomes important to develop a NPs design strategy that capitalizes on the NanoEL effect while averting unwanted side effects during the drug delivery process. Herein, we introduce the PLGA-ICG-PEI-Ang1@M NP which has a core comprising poly (lactic-co-glycolic acid) (PLGA) and the inner shell with a highly positively charged polyethyleneimine (PEI) and the anti-permeability growth factor Angiopoietin 1 (Ang1), while the outer shell is camouflaged with a Jurkat cell membrane. During the drug delivery process, our NPs exhibit their capability to selectively target and penetrate endothelial cell layers. Once the NPs penetrate the endothelial layer, the proton sponge effect triggered by PEI in the acidic environment surrounding the tumor site can rupture the cell membrane on the NPs' surface. This rupture, in turn, enables the positively charged Ang1 to be released due to the electrostatic repulsion from PEI and the disrupted endothelial layer can be restored. Consequently, the designed NPs can penetrate endothelial layers, promote the cell layer recovery, restrict the tumor metastasis, and facilitate efficient cancer therapy. STATEMENT OF SIGNIFICANCE.
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Nanopartículas , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Poliglicólico/farmacología , Ácido Láctico/farmacología , Línea Celular Tumoral , Células EndotelialesRESUMEN
BACKGROUND: The causal relationship and the direction of the effect between depression and aging remain controversial. METHODS: We used a bidirectional two-sample Mendelian randomization analysis to examine the relationship between depression and age proxy indicators. We obtained pooled statistics from genome-wide association studies (GWAS) on depression and the age proxy indicators. We employed five MR analysis methods to address potential biases and ensure robustness of our results, with the inverse variance weighted (IVW) method being the primary outcome. We also conducted outlier exclusion using Radial MR, MRPRESSO, and MR Steiger filters. Additionally, sensitivity analyses were performed to assess heterogeneity and pleiotropy. RESULTS: Our MR analysis revealed that depression causally leads to shortened telomere length (ß = - 0.014; P = 0.038), increased frailty index (ß = 0.076; P = 0.000), and accelerated GrimAge (ß = 0.249; P = 0.024). Furthermore, our findings showed that the frailty index (OR = 1.679; P = 0.001) was causally associated with an increased risk of depression. Additionally, we found that appendicular lean mass (OR = 0.929; P = 0.000) and left-hand grip strength (OR = 0.836; P = 0.014) were causally associated with a reduced risk of depression. Sensitivity analyses demonstrated the robustness of our findings. CONCLUSIONS: Our study provides evidence that depression contributes to the accelerated aging process, resulting in decreased telomere length, increased frailty index, and accelerated GrimAge. Additionally, we found that the frailty index increases the risk of depression, while appendicular lean mass and left-handed grip strength reduce the risk of depression.
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Depresión , Fragilidad , Humanos , Depresión/genética , Estudio de Asociación del Genoma Completo , Fuerza de la Mano , Análisis de la Aleatorización Mendeliana , Telómero , Acortamiento del Telómero , Envejecimiento/genéticaRESUMEN
Stem cell senescence is one of the most representative events of organism aging and is responsible for many physiological abnormalities and disorders. In the scenario of orthopedic disease treatment, stem cell aging may affect the implantation outcome and even lead to operation failure. To explore whether stem cell aging will affect the osteointegration effect of titanium implant, a widely used micronano titanium (MNT) was fabricated. We first verified the expected osteointegration effect of the MNT, which could be attributed to the improvement of stem cell adhesion and osteogenic differentiation. Then, we obtained aged-derived bone marrow mesenchymal stem cells (BMSCs) and studied their biological behaviors on MNT both in vitro and in vivo. We found that compared with normal rats, MNT did not significantly improve the osteointegration in aged rats. Compared with normal rats, fewer endogenous stem cells were observed at the implant-host interface, and the expression of p21 (senescence marker) was also higher. We further confirmed that MNT promoted the nuclear localization of NF-κB in senescent stem cells through the activation of p38 MAPK, thereby inducing the occurrence of the senescence-associated secretory phenotype (SASP) and ultimately leading to the depletion of the stem-cell pool at the implant-host interface. However, the activation of p38 MAPK can still promote the osteogenic differentiation of nonsenescent BMSCs. These results showed an interesting paradoxical balance between osteogenesis and senescence on MNT surfaces and also provided insights for the design of orthopedic implants for aging patients.
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Células Madre Mesenquimatosas , Titanio , Ratas , Humanos , Animales , Anciano , Titanio/farmacología , Titanio/metabolismo , Fenotipo Secretor Asociado a la Senescencia , Osteogénesis , Diferenciación Celular , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/farmacología , Células CultivadasRESUMEN
BACKGROUND: Gene knock-in (KI) in animal cells via homology-directed repair (HDR) is an inefficient process, requiring a laborious work for screening from few modified cells. HDR tends to occur in the S and G2/M phases of cell cycle; therefore, strategies that enhance the proportion of cells in these specific phases could improve HDR efficiency. RESULTS: We used various types of cell cycle inhibitors to synchronize the cell cycle in S and G2/M phases in order to investigate their effect on regulating CRISPR/Cas9-mediated HDR. Our results indicated that the four small molecules-docetaxel, irinotecan, nocodazole and mitomycin C-promoted CRISPR/Cas9-mediated KI with different homologous donor types in various animal cells. Moreover, the small molecule inhibitors enhanced KI in animal embryos. Molecular analysis identified common signal pathways activated during crosstalk between cell cycle and DNA repair. Synchronization of the cell cycle in the S and G2/M phases results in CDK1/CCNB1 protein accumulation, which can initiate the HDR process by activating HDR factors to facilitate effective end resection of CRISPR-cleaved double-strand breaks. We have demonstrated that augmenting protein levels of factors associated with the cell cycle via overexpression can facilitate KI in animal cells, consistent with the effect of small molecules. CONCLUSION: Small molecules that induce cell cycle synchronization in S and G2/M phases promote CRISPR/Cas9-mediated HDR efficiency in animal cells and embryos. Our research reveals the common molecular mechanisms that bridge cell cycle progression and HDR activity, which will inform further work to use HDR as an effective tool for preparing genetically modified animals or for gene therapy.
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Metabolic reprogramming is a hallmark of cancers crucial for fulfilling the needs of energy, building blocks, and antioxidants to support tumor cells' rapid proliferation and to cope with the harsh microenvironment. Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family whose expression is up-regulated in various tumors, however, whether it is involved in tumor cell metabolic reprogramming remains unclear. Herein, we report that PBX3 is a positive regulator of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway (PPP). PBX3 promoted G6PD transcriptional activity in tumor cells by binding directly to its promoter, leading to PPP stimulation and enhancing the production of nucleotides and NADPH, a crucial reductant, thereby promoting nucleic acid and lipid biosynthesis while decreasing intracellular reactive oxygen species levels. The PBX3/G6PD axis also promoted tumorigenic potential in vitro and in vivo. Collectively, these findings reveal a novel function of PBX3 as a regulator of G6PD, linking its oncogenic activity with tumor cell metabolic reprogramming, especially PPP. Furthermore, our results suggested that PBX3 is a potential target for metabolic-based anti-tumor therapeutic strategies.
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Neoplasias Colorrectales , Glucosafosfato Deshidrogenasa , Humanos , Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Vía de Pentosa Fosfato/genética , Especies Reactivas de Oxígeno/metabolismo , Carcinogénesis , Neoplasias Colorrectales/genética , Microambiente TumoralRESUMEN
OBJECTIVE: Observational studies have suggested a link between telomere length (TL) and epilepsy, but the direction of the effect and whether it is causal or not is still being debated. The objective of this study was to investigate the causal relationship between TL and epilepsy using Mendelian randomization (MR) analysis. METHODS: We performed a bidirectional two-sample MR analysis using pooled statistics from genome-wide association studies (GWAS) of TL and epilepsy. Additionally, we conducted a replication analysis using data from another GWAS study on epilepsy to validate our findings. The final results were analyzed using five MR methods, with the inverse-variance weighted (IVW) method as the primary outcome. We applied methods such as radial MR, MR pleiotropy residual and outlier test and MR Steiger filters to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy. RESULTS: Our analysis found no evidence of a causal relationship between epilepsy and TL (all p-values >0.05). The sensitivity analysis confirms the robustness of these results. SIGNIFICANCE: In summary, our study contradicts existing observational reports by not finding any evidence to support a causal relationship between epilepsy and TL. Further research is necessary to determine the underlying mechanism behind the association observed in observational studies.
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Epilepsia , Estudio de Asociación del Genoma Completo , Humanos , Análisis de la Aleatorización Mendeliana , Epilepsia/genética , Causalidad , Telómero/genéticaRESUMEN
Objectives: Physical activity (PA) is known to improve physical functioning and mental health and to reduce the incidence of dementia. However, studies of the effects of non-recreational PA on the incidence of dementia, especially in East Asian populations, remain limited. In this study, we evaluate the association of doing housework with the risk of dementia among participants in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Methods: The analysis was conducted with data from 7,237 CLHLS participants age over 65 obtained in 2008/2009, 2011/2012, 2014, and 2018. The frequency of housework performance was classified into four groups. A Cox proportional-hazards model was used to examine the association of the baseline housework frequency with the incidence of dementia, with adjustment for demographic and socioeconomic characteristics and lifestyle and health conditions. Results: The adjusted multivariate model showed that the incidence of dementia was lower among participants who did housework almost every day than among those who rarely or never did housework (hazard ratio = 0.49; 95% confidence interval, 0.39-0.61). The subgroup and sensitivity analyses yielded similar results. Conclusion: A high frequency of housework performance was associated with a reduced incidence of dementia among older Chinese adults, especially those who did not exercise regularly. The encouragement of engagement in housework would be a cost-effective measure promoting healthy aging in the Chinese population.
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Cancer stem cells (CSCs) are associated with tumor progression, recurrence, and therapeutic resistance. To maintain their pool while promoting tumorigenesis, CSCs divide asymmetrically, producing a CSC and a highly proliferative, more differentiated transit-amplifying cell. Exhausting the CSC pool has been proposed as an effective antitumor strategy; however, the mechanism underlying CSC division remains poorly understood, thereby largely limiting its clinical application. Here, through cross-omics analysis, yin yang 2 (YY2) is identified as a novel negative regulator of CSC maintenance. It is shown that YY2 is downregulated in stem-like tumor spheres formed by hepatocarcinoma cells and in liver cancer, in which its expression is negatively correlated with disease progression and poor prognosis. Furthermore, it is revealed that YY2 overexpression suppressed liver CSC asymmetric division, leading to depletion of the CSC pool and decreased tumor-initiating capacity. Meanwhile, YY2 knock-out in stem-like tumor spheres caused enrichment in mitochondrial functions. Mechanistically, it is revealed that YY2 impaired mitochondrial fission, and consequently, liver CSC asymmetric division, by suppressing the transcription of dynamin-related protein 1. These results unravel a novel regulatory mechanism of mitochondrial dynamic-mediated CSCs asymmetric division and highlight the role of YY2 as a tumor suppressor and a therapeutic target in antitumor treatment.
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Neoplasias Hepáticas , Dinámicas Mitocondriales , Humanos , Yin-Yang , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Línea Celular , Células Madre Neoplásicas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Metabolic reprogramming is one of the key features of tumors facilitating their rapid proliferation and adaptation to harsh microenvironments. Yin Yang 2 (YY2) has recently been reported as a tumor suppressor downregulated in various types of tumors; however, the molecular mechanisms underlying its tumor-suppressive activity remain poorly understood. Furthermore, the involvement of YY2 in tumor cell metabolic reprogramming remains unclear. Herein, we aimed to elucidate the novel regulatory mechanism of YY2 in the suppression of tumorigenesis. Using transcriptomic analysis, we uncovered an unprecedented link between YY2 and tumor cell serine metabolism. YY2 alteration could negatively regulate the expression level of phosphoglycerate dehydrogenase (PHGDH), the first enzyme in the serine biosynthesis pathway, and consequently, tumor cell de novo serine biosynthesis. Mechanistically, we revealed that YY2 binds to the PHGDH promoter and suppresses its transcriptional activity. This, in turn, leads to decreased production of serine, nucleotides, and cellular reductants NADH and NADPH, which subsequently suppresses tumorigenic potential. These findings reveal a novel function of YY2 as a regulator of the serine metabolic pathway in tumor cells and provide new insights into its tumor suppressor activity. Furthermore, our findings suggest the potential of YY2 as a target for metabolic-based antitumor therapeutic strategies.
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Fosfoglicerato-Deshidrogenasa , Serina , Humanos , Fosfoglicerato-Deshidrogenasa/genética , Fosfoglicerato-Deshidrogenasa/metabolismo , Línea Celular Tumoral , Yin-Yang , Carcinogénesis/genética , Microambiente Tumoral , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVE: Observational studies have shown an association between 25-hydroxyvitamin D (25 (OH) D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25 (OH) D levels and epilepsy. METHODS: We conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25 (OH) D levels and epilepsy using pooled statistics from genome-wide association studies (GWAS). Data for 25 (OH) D came from a GWAS comprising 417,580 participants, and data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium. Five methods were used to analyze TSMR, including the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In the sensitivity analysis, MR Egger and MR PRESSO methods were used to test for pleiotropy, inverse variance weighting and MR Egger in Cochran's Q statistics were used to test for heterogeneity. RESULTS: MR analyzed the relationship between 25 (OH) D and different types of epilepsy, and the results showed that a 1 standard deviation increase in natural log-transformed serum 25 (OH) D levels was associated with reduced risk for juvenile absence epilepsy (IVW OR = 0.985; 95% confidence interval [CI]: 0.971-0.999; P-value = 0.038). There was no apparent heterogeneity and horizontal gene pleiotropy. SIGNIFICANCE: Higher serum levels of 25 (OH) D were a protective factor for adolescent absence epilepsy, but had no effect on other types of epilepsy.
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Epilepsia Tipo Ausencia , Estudio de Asociación del Genoma Completo , Adolescente , Humanos , Análisis de la Aleatorización Mendeliana , Vitamina D , CalcifediolRESUMEN
Background: Non-suicidal self-injury (NSSI) is commonly seen in adolescents with depression and is a high-risk factor leading to suicide. The psychological mechanisms underlying depression with NSSI are still unclear. The purpose of this study was to explore the differences in personality traits, defensive styles, and borderline symptoms among first-episode youth patients with depression and self-injury compared with patients with depression without self-injury and healthy populations. Methods: The current study recruited 188 participants, including 64 patients with depression and NSSI, 60 patients with depression without NSSI, and 64 healthy control subjects. Eysenck Personality Questionnaire, the Defense Style Questionnaire, the short version of the Borderline Symptom List, the Beck Depression Inventory, and the Ottawa Self-Injury Inventory were used to assess all participants. Results: Patients with depression and NSSI showed more psychoticism than patients with depression without NSSI and healthy control subjects. Patients with depression and NSSI presented more intermediate defense styles than healthy control subjects. In the patients with depression and NSSI group, the frequency of self-injury in the last week was negatively correlated with mature defense styles and positively correlated with depressive symptoms and borderline symptoms. Further regression analysis showed that EPQ-psychoticism and depressive symptoms were independent risk factors for NSSI in patients with depression. Conclusion: This study found that patients with depression and self-injury presented more neuroticism, introversion, EPQ-psychoticism, immature defenses, intermediate defenses, and borderline symptoms. Self-injury frequency was negatively correlated with mature defense styles and positively correlated with depressive symptoms and borderline symptoms. EPQ-Psychoticism and depressive symptoms are risk factors for predicting non-suicidal self-injury in patients with depression.
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OBJECTIVE: To systematically evaluate the effectiveness and potential underlying mechanisms of acupuncture in the treatment of experimental model of migraine in rats. METHODS: Nine electronic databases, including CNKI (China National Knowledge Infrastructure), WanFang, VIP (Chinese Scientific Journals Database), Sinomed, PubMed, Cochrane Library, Web of Science and EBSCO, were searched for randomized experimental studies on migraine in rats involving acupuncture intervention. The search period ranged from inception to June 2022. The methodological quality was assessed using the SYRCLE's risk of bias tool for animal studies. Data were analyzed using the Revman 5.3 software. RESULTS: A total of 13 studies were included in this analysis. Findings from the available experimental studies documented that acupuncture significantly reduced behavior scores of rats with migraine (MD = -15.01, 95%CI = [-18.01, -12.01], P<0.00001) and downregulated the expression of calcitonin gene-related peptide (CGRP) (MD = -16.14, 95%CI = [-21.45, -10.83], P<0.00001), substance P (SP) (MD = -11.47, 95%CI = [-15.97, -6.98], P<0.00001) and nitric oxide (NO) (MD = -3.02, 95%CI = [-3.79, -2.26], P<0.00001) in serum, and stimulatory G protein (Gsa) (MD = -62.90, 95%CI = [-69.88, -55.92], P<0.00001) in brainstem. Acupuncture also significantly increased the content of inhibitory G protein (Gia) (MD = 24.01, 95%CI = [20.10, 27.92], P<0.00001) in brainstem and 50% paw withdrawal threshold (50%PWT) (MD = 1.96, 95%CI = [1.15, 2.77], P<0.00001). CONCLUSION: Acupuncture can effectively improve the behavioral performance of rates with migraine, and its mechanism of action might involve the inhibition of meningeal vasodilation and inflammatory factors, and the reduction of neurogenic inflammation.
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Terapia por Acupuntura , Trastornos Migrañosos , Ratas , Animales , Trastornos Migrañosos/terapia , Péptido Relacionado con Gen de Calcitonina , China , Proteínas de Unión al GTPRESUMEN
Protein corona formation can lead to obstructive screening of targeting groups of nanoparticles (NPs). Also, the targeting groups are subjected to physiochemical interactions when exposed to solvents. Here, these two factors can influence NP targeting efficiency. Therefore, it is necessary to prepare a general method of preparing an anti-fouling NPs with protected targeting groups. Here, we designed α-amylase-starch double-layer coated poly (methyl methacrylate-co-acrylic acid) NPs (α-ams-SCMMA NPs), functionalized with aptamer targeting groups and doped with Tetrakis(para-hydraoxylphenyl) porphyrin (TPPOH) as a payload drug. Natural polysaccharide starch and enzyme α-amylase were applied here for thermo-sensitive activation of starch hydrolyzation in order to render the NPs' self-polishing from protein corona effects. During incubation with serum media, the protein corona was formed at the exterior shell of NPs, while the self-polishing process was activated to remove the "protein fouling" when the incubation temperature increased to 37 °C (body temperature). Mechanistically, the starch layer of α-ams-SCMMA NPs was readily hydrolysed by α-amylase, whereby the adsorbed protein corona could be efficiently eliminated and the targeting groups were then presented. With this unique self-polishing NP design, we believe our method can be applied for potential NP applications in cancer therepy due to excellent antifouling property and protected targeting groups.
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Nanopartículas , Corona de Proteínas , Corona de Proteínas/química , Polímeros , Amilasas , Almidón , Nanopartículas/química , alfa-AmilasasRESUMEN
Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) revealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue remodeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for organoid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.