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1.
Hematology ; 27(1): 1184-1190, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36318614

RESUMO

OBJECTIVES: Little is known about the clinical impact of germline/somatic mutations of PTPN11 in acute leukemia. The aim of this study was to investigate the clinical characteristics and prognostic impact of PTPN11 mutations in patients with acute myeloid leukemia (AML). METHODS: Seventy-four patients with PTPN11 mutation-positive AML treated at our institution were enrolled in this study. The prevalence of PTPN11 mutations was examined using targeted next-generation sequencing technology, and patients with AML and PTPN11 mutations were screened. Clinical characteristics, prognostic impact, and association between PTPN11 mutations and other mutations were analyzed retrospectively. RESULTS: PTPN11 mutations co-occurred more commonly with DNMT3A, NPM1, and FLT3 internal tandem duplication mutations. Compared with PTPN11 wild-type (WT) patients, PTPN11 mutation-positive AML patients presented with higher white blood cell (WBC) and platelet (PLT) counts. In 74 PTPN11 positive AML patients, PTPN11 mutations had an adverse effect on overall survival (OS) (62.5%) and a negative prognostic effect on event-free survival (EFS) (50%). Allo-hematopoietic stem cell transplantation (HSCT) abrogated the negative effect of mutations in PTPN11; the OS and EFS of AML patients with PTPN11 mutations who received transplantation were longer than those of AML patients with PTPN11 mutations who did not undergo allo-HSCT (P = 0.001, EFS; P < 0.001, OS). Discussion: Newly diagnosed PTPN11 mutation-positive AML patients with high WBC and PLT counts or presenting no remission after first induction chemotherapy suffer from high mortality rates. CONCLUSION: Given the lack of targeted therapies for PTPN11 mutations, timely HSCT is necessary for patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Prognóstico , Estudos Retrospectivos , Mutação , Tirosina Quinase 3 Semelhante a fms , Proteína Tirosina Fosfatase não Receptora Tipo 11
2.
Asian J Pharm Sci ; 17(5): 679-696, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36382300

RESUMO

Photodynamic therapy (PDT)-mediated oxidation treatment is extremely attractive for skin melanoma ablation, but the strong hydrophobicity and poor tumor selectivity of photosensitizers, as well as the oxygen-consuming properties of PDT, leading to unsatisfactory therapeutic outcomes. Herein, a tumor acidic microenvironment activatable dissolving microneedle (DHA@HPFe-MN) was developed to realize controlled drug release and excellent chemo-photodynamic therapy of melanoma via oxidative stress amplification. The versatile DHA@HPFe-MN was fabricated by crosslinking a self-synthesized protoporphyrin (PpIX)-ADH-hyaluronic acid (HA) conjugate HA-ADH-PpIX with "iron reservoir" PA-Fe3+ complex in the needle tip via acylhydrazone bond formation, and dihydroartemisinin (DHA) was concurrently loaded in the hydrogel network. HA-ADH-PpIX with improved water solubility averted undesired aggregation of PpIX to ensure enhanced PDT effect. DHA@HPFe-MN with sharp needle tip, efficient drug loading and excellent mechanical strength could efficiently inserted into skin and reach the melanoma sites, where the acidic pH triggered the degradation of microneedles, enabling Fe-activated and DHA-mediated oxidation treatment, as evidenced by abundant reactive oxygen species (ROS) generation. Moreover, under light irradiation, a combined chemo-photodynamic therapeutic effect was achieved with amplified ROS generation. Importantly, the Fe-catalyzed ROS production of DHA was oxygen-independent, which work in synergy with the oxygen-dependent PDT to effectively destroy tumor cells. This versatile microneedles with excellent biosafety and biodegradability can be customized as a promising localized drug delivery system for combined chemo-photodynamic therapy of melanoma.

3.
Ticks Tick Borne Dis ; 14(1): 102082, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36403321

RESUMO

Haemaphysalis longicornis is one of the most dominant and widespread tick species in China. This species mainly infests wild animals and occasionally attacks humans, and has been associated with the transmission of a variety of zoonotic pathogens including spotted fever group Rickettsia (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV), Anaplasma phagocytophilum, Babesia spp. and Theileria spp.. Although there are increasing reports of various pathogens associated with H. longicornis, some neglected pathogens in certain areas still need to be studied. In this study, a total of 171 H. longicornis ticks were collected from goats in three locations of Shandong Province, Eastern China (Zibo, Linyi, and Qingdao cities), and subsequently screened for the presence of Rickettsia, Anaplasma, and Ehrlichia bacteria. A total of four bacterial species were identified and characterized. "Candidatus Rickettsia jingxinensis" was detected in one tick specimen from Zibo city. Of 98 ticks from Linyi city, 63.27% (62/98) were tested positive for Anaplasma capra and 5.10% (5/98) were positive for Anaplasma bovis. Interestingly, a novel Anaplasma species was detected and characterized in one tick specimen from Zibo and one other from Linyi, respectively. Genetic and phylogenetic analysis based on the 16S, gltA, groEL, and msp4 genes indicated that it was divergent from all known Anaplasma species but mostly related to A. phagocytophilum and "Cadidatus Anaplasma boleense". Based on where it was first detected, we named it "Candidatus Anaplasma shandongensis".

4.
Foods ; 11(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36359945

RESUMO

High-quality wines in industrial winemaking frequently require a professional winemaker to make adjustments according to the wine of single-batch fermentation. Blending can improve the chemical composition and certain organoleptic properties of wine, promote copigmentation, and increase the complexity of the wine body and aroma. In this study, high-performance liquid chromatography (HPLC) and headspace solid-phase microextraction with gas chromatography coupled to tandem mass spectrometry (HS-SPME-GC-MS/MS) were used to study the effects of adding 20% of Merlot, Marselan, Syrah and Pinot Noir and different blending methods on the nutritional, taste, color and aroma components of Cabernet Sauvignon wine. The results showed that the highest total phenols and flavonoids, the greatest content of antioxidant characteristics, the optimal color according to the parameter of T, red% and blue% and the most abundant aroma were observed both in CGM (grape blending Cabernet Sauvignon and Merlot) and CGS (grape blending Cabernet Sauvignon and Marselan), thus indicating the higher quality and complexity of these wines. In addition, the co-grapes treatment afforded more color and hue value than co-wines, which indicates co-grapes had more stable and more varied colors than co-wines. Our findings provide theoretical support for improving wine quality and craftsmanship.

5.
J Bone Miner Res ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36321245

RESUMO

Age-related bone loss is a failure of balanced bone turnover and diminished skeletal mechanoadaptation. Estrogen receptors, ERα and ERß, play critical roles in osteoprotective regulation activated by estrogen and mechanical signals. Previous studies mainly focused on ERα and showed that osteocyte-ERα (Ot-ERα) regulated trabecular but not cortical bone and played a minor role in load-induced cortical adaptation. However, the role of Ot-ERß in bone mass regulation remains unrevealed. To address this issue, we characterized bone (re)modeling and gene expression in male and female mice with Ot-ERß deletion (ERß-dOT) and littermate control (LC) at 10wk (young) or 28wk (adult) of age, as well as their responses to in vivo tibial compressive loading. Increased cancellous bone mass appeared in the L4 vertebral body of young male ERß-dOT mice. At the same time, femoral cortical bone gene expression showed signs consistent with elevated osteoblast and osteoclast activities (Type-I collagen, CatK, RANKL). Upregulated androgen receptor (AR) expression was observed in young male ERß-dOT mice relative to LC, suggesting a compensatory effect of testosterone on male bone protection. In contrast, bone mass in L4 decreased in adult male ERß-dOT mice, attributed to potentially increased bone resorption activity (Cat K) with no change in bone formation. There was no effect of ERß-dOT on bone mass or gene expression in female mice. Sex-dependent regulation of Ot-ERß also appeared in load-induced cortical responsiveness. Young female ERß-dOT mice showed an enhanced tibial cortical anabolic adaptation compared to LC. In contrast, an attenuated cortical anabolic response presented at the proximal tibia in male ERß-dOT mice at both ages. For the first time, our findings suggest that Ot-ERß regulates bone (re)modeling and the response to mechanical signals through different mechanisms in males and females.

6.
Front Aging Neurosci ; 14: 974690, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389075

RESUMO

Background: Diabetes-associated cognitive impairment (DACI) is a common complication of diabetes, and studies have shown that DACI is more severe in postmenopausal patients with diabetes. Forsythoside B (FTS⋅B) can inhibit inflammation and reduce synaptic dysfunction, which can improve cognitive function. However, it has not been confirmed whether FTS⋅B has a reversing or retarding effect on postmenopausal diabetic encephalopathy. Methods: Seven days after bilateral ovariectomy (OVX) or sham surgery, adult female C57 mice (n = 15/group) received intraperitoneal injection of streptozotocin (60 mg/kg/day/L) and citrate buffer for 5 consecutive days to induce diabetes mellitus (DM). Fourteen days later, ovariectomized diabetic mice were given intraperitoneal injection of FTS⋅B (100, 150 mg/kg/day/L) and subcutaneous injection of 17ß-estradiol (1 mg/kg) for 8 weeks [OVX + DM + low-FTS⋅B group (L-F), OVX + DM + high-FTS⋅B group (H-F), and OVX + DM + 17ß-estradiol (ER)]. In addition, the following control groups were defined: Sham, OVX, DM, and OVX + DM (O + D). Fasting plasma glucose, body weight and blood insulin levels were determined in each group of mice. Next, their cognitive function was tested through behavioral experiments. Hematoxylin & eosin (H&E) and Nissl staining were used to detect the morphological changes in the hippocampus. The aggregation of amyloid beta (Aß) and the hyperaggregation of p-tau were assessed by immunohistochemistry. Interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), post-synaptic density-95 (PSD-95), synaptophysin, and synapsin-1 expression in the hippocampus was detected by real-time polymerase chain reaction (RT-PCR) and western blot analysis. Results: FTS⋅B can decrease fasting glucose and blood insulin level. Behavioral results showed that cognitive decline was the most severe in the O + D group, and the ER, L-F, and H-F groups revised the cognitive decline. Compared to the O + D group, more normal morphology, which has obvious nucleoli and clear nuclear membrane, was observed by H&E and Nissl staining in the ER, L-F, and H-F groups. FTS⋅B alleviated DACI by reducing the aggregation of Aß and the hyperaggregation of p-tau in the hippocampus. Moreover, the protein and mRNA expression showed that FTS⋅B not only inhibited inflammation by decreasing IL-1ß, IL-6, and TNF-α but also modulated synaptic plasticity by increasing BDNF, PSD-95, synaptophysin, and synapsin-1. Conclusion: These results suggest that FTS⋅B may be a novel therapeutic target for postmenopausal diabetic encephalopathy treatment.

7.
Mikrochim Acta ; 189(12): 475, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434295

RESUMO

A sensitive, accurate, and rapid multimode dot-filtration immunoassay (MDFIA) was established for the detection of Salmonella typhimurium using the intrinsic color, catalytic property, and photothermal effect of magnetic molybdenum disulphide (MoS2@Fe3O4). The critical performance parameters of MDFIA were optimized in detail. The sensitivity of MDFIA can be improved by the catalytic color development and photothermal conversion of MoS2@Fe3O4 with a limit of detection (LOD) of 101 CFU·mL-1, which is an order of magnitude lower than direct visual detection (102 CFU·mL-1). Besides, the magnetic property of MoS2@Fe3O4 was used for the rapid enrichment and separation of the target allowing detection of trace concentrations of Salmonella typhimurium. The selectivity and applicability of the MDFIA were verified in spiked samples, indicating that the established assay may have bright application prospects for the detection and control of foodborne pathogens. A multimode dot-filtration immunoassay was constructed for Salmonella typhimurium rapid detection based on the peroxidase-like activity, magnetic property, and photothermal effect of MoS2@Fe3O4.


Assuntos
Microbiologia de Alimentos , Salmonella typhimurium , Molibdênio , Limite de Detecção , Imunoensaio
8.
Biomolecules ; 12(11)2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36421715

RESUMO

Rickettsiales (Rickettsia spp., Ehrlichia spp., and Anaplasma spp., etc.) are generally recognized as potentially emerging tick-borne pathogens. However, some bacteria and areas in China remain uninvestigated. In this study, we collected 113 ticks from mammals in Guizhou Province, Southwest China, and screened for the Rickettsiales bacteria. Subsequently, two spotted fever group Rickettsia species and one Candidatus Lariskella sp. were detected and characterized. "Candidatus Rickettsia jingxinensis" was detected in Rhipicephalus microplus (1/1), Haemaphysalis flava (1/3, 33.33%), Haemaphysalis kitaokai (1/3), and Ixodes sinensis (4/101, 3.96%), whereas Rickettsia monacensis was positive in H. flava (1/3), H. kitaokai (2/3), and I. sinensis ticks (74/101, 73.27%). At least two variants/sub-genotypes were identified in the R. monacensis isolates, and the strikingly high prevalence of R. monacensis may suggest a risk of human infection. Unexpectedly, a Candidatus Lariskella sp. belonging to the family Candidatus Midichloriaceae was detected from Ixodes ovatus (1/4) and I. sinensis (10/101, 9.90%). The gltA and groEL gene sequences were successfully obtained, and they show the highest (74.63-74.89% and 73.31%) similarities to "Candidatus Midichloria mitochondrii", respectively. Herein, we name the species "Candidatus Lariskella guizhouensis". These may be the first recovered gltA and groEL sequences of the genus Candidatus Lariskella.


Assuntos
Ixodes , Rickettsia , Rickettsiose do Grupo da Febre Maculosa , Humanos , Animais , Prevalência , Rickettsia/genética , Rickettsiales , China , Rickettsiose do Grupo da Febre Maculosa/epidemiologia , Mamíferos
9.
Front Neurol ; 13: 1052310, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419529

RESUMO

Approximately 50-60% of patients with a clinical transient ischemic attack (TIA) do not have diffusion-weighted imaging (DWI) evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of diffusion kurtosis imaging (DKI) in the evaluation of patients with TIA who have normal DWI findings. From September 2014 to May 2017, a total of 179 consecutive patients with suspected TIA were eligible for enrollment in our study. The inclusion criteria were a confirmed diagnosis of TIA confirmed by a stroke neurologist, MRI (including DWI and DKI) within 24 h after symptom onset, no stroke history, and no DWI lesion. A follow-up DWI was performed to establish stroke recurrence within a period of 90 days. A total of 98 patients who had no lesions on the baseline DWI were included for data analysis. Of these 98 patients, 31 (31.6%) had positive findings on the initial DKI. In 29 of the 31 (93.5%) patients, the location of the abnormality observed on DKI was consistent with the clinical symptoms. During the 90-day follow-up period, 14 (14.3%) patients developed recurrent stroke. The prevalence of recurrent stroke was higher in the DKI-positive group than in the DKI-negative group (29.0% vs. 7.5%, p = 0.01). A comparison between the patients with and without recurrent stroke showed that an abnormality on the baseline DKI was associated with stroke recurrence. Furthermore, 8 of the 9 stroke patients in the DKI-positive group developed a new ischemic lesion in the artery territory corresponding to the initial DKI abnormality. The new findings suggest the predictive value of DKI on the recurrence of stroke in the patients with TIA who have negative findings on conventional DWI.

10.
Adv Mater ; : e2208578, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36440662

RESUMO

Sepsis, a widely recognized disease, is characterized by multiple pathogen infections. Therefore, it is imperative to develop methods that can efficiently identify and neutralize pathogen species. Phage cocktail therapy utilizes the host specificity of phages to adapt to infect resistant bacteria. However, its low sterilization stability efficiency and lack of imaging units seriously restrict its application. Here, we propose a novel strategy combining the aggregation-induced emission photosensitizer (AIE-PS) TBTCP-PMB with phages through a nucleophilic substitution reaction between benzyl bromide and sulfhydryl groups to remove pathogenic bacteria for sepsis treatment. This strategy retains the phage's host specificity while possessing AIE-PS characteristics with a fluorescence imaging function and reactive-oxygen-species (ROS) for detecting and sterilizing bacteria. This synergetic strategy combining phage cocktail therapy and photodynamic therapy (PDT) showed a strong "1+1>2" bactericidal efficacy and superior performance in sepsis mouse models with good biocompatibility. Furthermore, the strategy can quickly diagnose blood infections of clinical blood samples. This simple and accurate strategy provides a promising therapeutic platform for rapid pathogen detection and point-of-care diagnosis. Moreover, it presents a new method for expanding the library of antibacterial drugs to develop new strain identification and improve infectious disease treatment, thereby demonstrating strong translational potential. This article is protected by copyright. All rights reserved.

11.
J Clin Lab Anal ; : e24772, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36441595

RESUMO

BACKGROUND: According to the randomized multicenter phase II trial (ALTER1202), anlotinib has been approved as a third-line therapy for advanced small-cell lung cancer (SCLC). Some studies showed the predictive function of inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in the different cancers treated with anti-vascular targeting drugs. However, none of the studies showed the roles of NLR, PLR, and LMR in SCLC patients receiving anlotinib. Thus, our objective was to establish a scoring system based on inflammation to individuate patient stratification and selection based on NLR, PLR, and LMR. METHODS: NLR, PLR, and LMR and their variations were calculated in 53 advanced SCLC patients receiving anlotinib as a third- or further-line treatment at Ningbo Medical Center Lihuili Hospital between January 2019 and December 2021. Kaplan-Meier curves were plotted. Both univariate and multivariate Cox regressions were used to identify predictors of survival. RESULTS: Disease control rate was related to pre-NLR, pre-PLR, pre-LMR, post-NLR elevation, post-PLR elevation, and post-LMR elevation. The multivariate analysis determined post-NLR elevation, pre-PLR > 240.56, and pre-LMR ≤1.61 to be independently associated with progression-free survival, not overall survival. The inflammation-based prognostic scoring system demonstrated favorable predictive ability from the receiver operating characteristic curve (AUC: 0.791, 95% CI: 0.645-0.938). CONCLUSIONS: Post-NLR variation, pre-PLR, and pre-LMR were independent prognostic factors for PFS in advanced SCLC receiving anlotinib monotherapy. The inflammation-based prognostic scoring system can accurately predict effectiveness and survival.

12.
Nanoscale ; 14(42): 15832-15844, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36255392

RESUMO

Ribonucleoprotein (RNP) based CRISPR/Cas9 gene-editing system shows great potential in biomedical applications. However, due to the large size, charged surface and high biological sensitivity of RNP, its efficient delivery with precise control remains highly challenging. Herein, a microfluidic-assisted metal-organic framework (MOF) based biomineralization strategy is designed and utilized for the efficient delivery and remote regulation of CRISPR/Cas9 RNP gene editing. The strategy is realized by biomimetic growing of thermo-responsive EuMOFs onto photothermal template Prussian blue (PB). The RNP is loaded during MOFs crystallization in microfluidic channels. By adjusting different microfluidic parameters, well-defined and comparable RNP encapsulated nanocarrier (PB@RNP-EuMOFs) are obtained with high loading efficiency (60%), remarkable RNP protection and NIR-stimulated release capacity. Upon laser exposure, the nanocarrier induces effective endosomal escape (4 h) and precise gene knockout of green fluorescent protein by 40% over 2 days. Moreover, the gene-editing activity can be programmed by tuning exposure times (42% for three times and 47% for four times), proving more controllable and inducible editing modality compared to control group without laser irradiation. This novel microfluidic-assisted MOFs biomineralization strategy thus offers an attractive route to optimize delivery systems and reduce off-target side effects by NIR-triggered remote control of CRISPR/Cas9 RNP, improving the potential for its highly efficient and precise therapeutic application.


Assuntos
Edição de Genes , Estruturas Metalorgânicas , Sistemas CRISPR-Cas , Estruturas Metalorgânicas/metabolismo , Microfluídica , Biomineralização , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo
13.
Front Immunol ; 13: 1007610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275747

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint destruction, synovitis, and pannus formation. Gut microbiota dysbiosis may exert direct pathogenic effects on gut homeostasis. It may trigger the host's innate immune system and activate the "gut-joint axis", which exacerbates the RA. However, although the importance of the gut microbiota in the development and progression of RA is widely recognized, the mechanisms regulating the interactions between the gut microbiota and the host immune system remain incompletely defined. In this review, we discuss the role of gut microbiota-derived biological mediators, such as short-chain fatty acids, bile acids, and tryptophan metabolites, in maintaining intestinal barrier integrity, immune balance and bone destruction in RA patients as the bridge of the gut-joint axis.


Assuntos
Artrite Reumatoide , Microbioma Gastrointestinal , Humanos , Triptofano , Ácidos Graxos Voláteis , Ácidos e Sais Biliares
14.
J Clin Sleep Med ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36305585

RESUMO

STUDY OBJECTIVES: To quantitatively evaluate the influence of obstructive sleep apnea syndrome (OSAS) on the morphology and function of the contralateral optic nerve in patients with unilateral nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: Fifty patients with unilateral NAION were divided into non-OSAS (n=16), mild (n=15), and moderate-severe (n=19) groups based on their apnea hypopnea index (AHI) scores. Systemic and ocular characteristics were compared between these groups. Spearman correlation and multiple linear regression analyses were used to determine the independent factors that most influenced the thickness of the peripapillary retinal nerve fiber layer (pRNFL). RESULTS: Body mass index and hypertension occurrence were higher in the moderate-severe OSAS group than in the non-OSAS group. Temporal pRNFL was thinner in the moderate-severe group than in the mild and non-OSAS groups, while no difference was found between the mild and non-OSAS groups. Spearman correlation showed that the AHI (r = -0.469, P = 0.001) and the percentage of total sleep time with oxygen saturation < 90% (T90%, r=-0.477, P=0.001) correlated with temporal pRNFL thickness. Multiple linear regression showed that the AHI was negatively associated to temporal pRNFL thickness (B = -0.573, P = 0.003). CONCLUSIONS: OSAS may cause subclinical temporal pRNFL thinning in the contralateral optic nerve among patients with unilateral NAION without any significant change in visual function. Advanced optic nerve observation and intervention may be warranted in patients with moderate-severe OSAS.

15.
Am J Hematol ; 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36219502

RESUMO

Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36248435

RESUMO

Background: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by progressive oral and ocular dryness that correlates poorly with autoimmune damage to the glands. CheReCunJin (CRCJ) formula is a prescription formulated according to the Chinese medicine theory for SS treatment. Objective: This study aimed to explore the underlying mechanisms of CRCJ against SS. Methods: The databases, including Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine, Bioinformatics Analysis Tool for the molecular mechanism of Traditional Chinese Medicine, and Traditional Chinese Medicine Integrated Databases, obtained the active ingredients and predicted targets of CRCJ. Then, DrugBank, Therapeutic Target Database, Genecards, Comparative Toxicogenomics Database, and DisGeNET disease databases were used to screen the predicted targets of SS. Intersected targets of CRCJ and SS were visualized by using Venn diagrams. The overlapping targets were uploaded to the protein-protein interaction network analysis search tool. Cytoscape 3.8.2 software constructed a "compound-targets-disease" network. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses characterized potential targets' biological functions and pathways. AutoDock Vina 1.1.2 software was used to research and verify chemical effective drug components and critical targets. Results: From the database, we identified 878 active components and 2578 targets of CRCJ, and 827 SS-related targets. 246 SS-related genes in CRCJ were identified by intersection analysis, and then ten hub genes were identified as crucial potential targets from PPI, including ALB, IL-6, TNF, INS, AKT1, IL1B, VEGFA, TP53, JUN, and TLR4. The process of CRCJ action against SS was mainly involved in human cytomegalovirus infection and Th17 cell differentiation, as well as the toll-like receptor signaling and p53 signaling pathways. Molecular docking showed that the bioactive compounds of CRCJ had a good binding affinity with hub targets. Conclusions: The results showed that CRCJ could activate multiple pathways and treat SS through multiple compounds and targets. This study lays a foundation for better elucidation of the molecular mechanism of CRCJ in the treatment of SS, and also provides basic guidance for future research on Chinese herbal compounds.

18.
Front Psychol ; 13: 989463, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225703

RESUMO

Customers' declining receptivity to conventional marketing tools has been a challenge for convenience stores. To overcome this, retailers are turning to social media as a new, potent marketing tool for creating business prospects and encouraging direct customer interaction. However, it is still unknown how social media marketing affects the shifts in customer behavior. This paper expands on the relationship of "loyalty program (LP) + virtual community experience → perceived value → customer loyalty" in the traditional convenience store scenario, refining the variables of virtual community experience, perceived value, and customer loyalty. It also compares the effectiveness of different LP design structures (reward amounts × reward time limits) and explores the mediation impact of program loyalty and the moderation effect of alternative attractiveness. The results demonstrate the superior performance of LPs with an expiry policy and differential returns and highlight the importance of enhancing members' virtual community experiences in fostering customer perceived value and loyalty. The results also show the minor negative moderation impact of community group buying and prove that emotional value significantly impacts customer loyalty. Still, the social value does not affect program loyalty. The recommendations are offered, such as designing growing-oriented and periodical zeroing LPs, as well as using new social media marketing tools (virtual community-based marketing) to empower traditional marketing techniques (LP-based relationship marketing) and constructing a "convenience store + community group buying" model. The findings have substantial theoretical and practical implications for traditional convenience stores in properly implementing loyalty and social media marketing tactics to maximize customer value and loyalty with a limited budget.

19.
Molecules ; 27(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36144726

RESUMO

In vivo metabolism of polyethylene glycol (PEG) hydrogels has rarely been studied. In this study, we prepared a chemically crosslinked hydrogel formulation using 14C-labeled tetra-armed poly (ethylene glycol) succinimidyl succinate (Tetra-PEG-SS) and 3H-labeled crosslinking agent for implantation into the pelvis of Sprague-Dawley (SD) rats. This radioactive labeling technique was used to investigate the radioactivity excretion rates in of feces and urine, the blood exposure time curve, and the radioactivity recovery rate in each tissue over time. We showed that the primary excretion route of the hydrogel was via urine (3H: about 86.4%, 14C: about 90.0%), with fewer portion through feces (3H: about 6.922%, 14C: about 8.16%). The hydrogel metabolites exhibited the highest distribution in the kidney, followed by the jejunal contents; The 3H and 14C radioactivity exposures in the remaining tissues were low. We also showed that the 3H and 14C radioactivity recovery rates in the blood were usually low (<0.10% g-1 at 12 h after implantation), even though, in theory, the hydrogel could be absorbed into the blood through the adjacent tissues. By using a combination of HPLC-MS/MS and offline radioactivity counting method, we established that the tetra-PEG-based hydrogel was mainly metabolized to lower-order PEG polymers and other low-molecular-weight substances in vivo.


Assuntos
Polietilenoglicóis , Espectrometria de Massas em Tandem , Animais , Materiais Biocompatíveis/química , Hidrogéis/química , Pelve , Polietilenoglicóis/química , Polímeros , Ratos , Ratos Sprague-Dawley , Succinatos
20.
Oxid Med Cell Longev ; 2022: 6293355, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160715

RESUMO

Dendrobium officinale has a long history of being consumed as a functional food and medicinal herb for preventing and managing diseases. The phytochemical studies revealed that Dendrobium officinale contained abundant bioactive compounds, such as bibenzyls, polysaccharides, flavonoids, and alkaloids. The experimental studies showed that Dendrobium officinale and its bioactive compounds exerted multiple biological properties like antioxidant, anti-inflammatory, and immune-regulatory activities and showed various health benefits like anticancer, antidiabetes, cardiovascular protective, gastrointestinal modulatory, hepatoprotective, lung protective, and neuroprotective effects. In this review, we summarize the phytochemical studies, bioactivities, and the mechanism of actions of Dendrobium officinale, and the safety and current challenges are also discussed, which might provide new perspectives for its development of drug and functional food as well as clinical applications.


Assuntos
Alcaloides , Bibenzilas , Dendrobium , Fármacos Neuroprotetores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Dendrobium/química , Flavonoides , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Polissacarídeos/química
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