Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 141
Filtrar
1.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678320

RESUMO

Essential oils (EO) are promising feed additives for their antibacterial, antioxidant, and immune-enhancing abilities with low toxicity. Carvacrol, thymol, and cinnamaldehyde are commonly used to synthesize EO. However, few studies focus on combining these three EO in early-weaned piglets. In the present study, 24 piglets weaned at 21 d of age were randomly divided into 2 groups (6 replicate pens per group, 2 piglets per pen). The piglets were fed a basal diet (the control group) and a basal diet supplemented with 400 mg/kg EO (a blend consisting of carvacrol, thymol, and cinnamaldehyde, the EO group) for 28 days. At the end of the experiment, one piglet per pen was randomly chosen to be sacrificed. Growth performance, hematology, plasma biochemical indices, antioxidant capacity, intestinal epithelial development and immunity, colonic volatile fatty acids (VFA), and microbiota were determined. The results indicated that the diet supplemented with EO significantly improved average daily feed intake (ADFI, p < 0.01) and average daily gain (ADG, p < 0.05) in the day 0 to 28 period. EO supplementation led to a significant decrease in plasma lysozyme (p < 0.05) and cortisol levels (p < 0.01). Additionally, EO significantly promoted jejunal goblet cells in the villus, jejunal mucosa ZO-1 mRNA expression, ileal villus height, and ileal villus height/crypt depth ratio in piglets (p < 0.05). The ileal mucosal TLR4 and NFκB p-p65/p65 protein expression were significantly inhibited in the EO group (p < 0.05). Colonic digesta microbiota analysis revealed that bacteria involving the Erysipelotrichaceae family, Holdemanella genus, Phascolarctobacterium genus, and Vibrio genus were enriched in the EO group. In conclusion, these findings indicate that the EO blend improves ADG and ADFI in the day 0 to 28 period, as well as intestinal epithelial development and intestinal immunity in early-weaned piglets, which provides a theoretical basis for the combined use of EO in weaned piglets.


Assuntos
Microbiota , Óleos Voláteis , Animais , Suínos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Óleos Voláteis/farmacologia , Timol/farmacologia , Suplementos Nutricionais
2.
Anim Biotechnol ; : 1-10, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36306258

RESUMO

Broodiness, a maternal behavior, is accompanied by the atresia of follicles and the serious degradation of poultry reproductive performance. The comparison of follicles between brooding and laying hens is usually an ideal model for exploring the regulation mechanism of follicle atresia. In this study, we selected three brooding hens and three laying hens to collect their follicles for whole transcriptome sequencing. The results demonstrated different expression patterns between the follicles of brooding hens and laying hens. In the top 10 differentially expressed genes with the highest expression, MMP10 was relatively low expressed in the follicles of brooding hens, but other nine genes were relatively highly expressed, including LRR1, RACK1, SPECC1L, ABHD2, COL6A3, RPS17, ATRN, BIRC6, PGAM1 and SPECC1L. While miR-21-3p, miR-146a-5p, miR-142-5p and miR-1b-3p were highly expressed in the follicles of brooding hen, miR-106-5p, miR-451, miR-183, miR-7, miR-2188-5p and miR-182-5p were lowly expressed in brooding hen. In addition, we identified 124 lncRNAs specifically expressed in the follicles of brooding hens and 147 lncRNAs specifically expressed in the follicles of laying hens. Our results may provide a theoretical basis for further exploration of the molecular mechanism of broodiness in broilers.

3.
Clin Cosmet Investig Dermatol ; 15: 2065-2075, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36196252

RESUMO

Background: Although the changed lipid environment of the pilosebaceous unit and the growth of lipophilic Cutibacterium acnes (C. acnes) during puberty has long been considered as the trigger of acne vulgaris, the involvement of the interaction between the epidermal barrier integrity and the skin microbiome in this disease has not been fully elucidated. Objective: The aim of this study was to analyze the differences in the epidermal barrier and skin microbiota in patients with acne vulgaris and their correlation. Methods: The skin microbial samples and epidermal barrier data from 74 acne patients and 19 healthy subjects were collected in this cross-sectional study. The microbial diversity was analyzed based on a high-throughput sequencing approach that targets the V3-V4 region of the bacteria 16S ribosomal RNA genes. Results: Compared with healthy controls, acne patients had significantly increased transepidermal water loss (TEWL), pH levels, sebum, porphyrins, and red areas, and reduced skin microbiome diversity according to the goods coverage diversity index (p = 0.021), Shannon diversity index (p = 0.037), and Simpson diversity index (p = 0.023). Moreover, the diversity gradually decreased with the increase in acne grading. Based on the principal coordinate analysis (PCoA) analysis plot, the skin microbiota of acne patients and healthy controls could be divided into two different sets, which could not be used to separate acne patients with different disease severity. Finally, this study found that both TEWL and sebum were negatively associated with the Shannon and Simpson diversity index. Meanwhile, the taxa Enhydrobacter and Stenotrophomonas were positively associated with TEWL, stratum corneum hydration, respectively. Conclusion: This study demonstrated that acne vulgaris exists in patients with both damaged epithelial barriers and associated microbiota dysbiosis; the findings will help improve the understanding of the disease and may contribute to the development of better treatment options.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36239896

RESUMO

Hydroxyapatite-coated quartz sands were synthesized by the sol-gel method and employed as a permeable reactive barrier (PRB) medium for the manganese contaminated aqueous solution treatment. The effects of composite particle size, initial concentration of manganese, and hydraulic load on the manganese removal in aqueous solution were investigated by column test. The Thomas and Yoon-Nelson dynamic models were used to reproduce the Mn(II) adsorption behavior observed in these column experiments. The scanning electron microscope (SEM) coupled with energy dispersive spectrometer (EDS), X-ray diffractometer (XRD), and X-ray photoelectron spectroscopy (XPS) were employed to investigate the Mn(II) removal mechanism. Results showed that the initial concentration of manganese had the greatest influence on Mn(II) removal when the initial concentration of manganese is 3 mg/L, the particle size is 0.15 ~ 0.3 mm, the hydraulic load is 5.5 m3/m2·d, and the adsorption capacity of the composites reached the maximum of 1.10 mg/g. The Thomas model fitted the breakthrough curves better. The maximum adsorption capacity of Mn(II) is 0.7546 mg/g. The adsorption mechanisms are mainly ion exchange and dissolution-precipitation. The results indicate that the hydroxyapatite-coated quartz sands could be an effective PRB media for the manganese-contaminated water treatment.

5.
Front Microbiol ; 13: 1008053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312981

RESUMO

It is difficult to treat malignant melanoma because of its high malignancy. New and effective therapies for treating malignant melanoma are urgently needed. Ergosterols are known for specific biological activities and have received widespread attention in cancer therapy. Here, LH-1, a kind of ergosterol from the secondary metabolites of the marine fungus Pestalotiopsis sp., was extracted, isolated, purified, and further investigated the biological activities against melanoma. In vitro experiments, the anti-proliferation effect on tumor cells was detected by MTT and colony formation assay, and the anti-metastatic effect on tumor cells was investigated by wound healing assay and transwell assay. Subcutaneous xenograft models, histopathology, and immunohistochemistry have been used to verify the anti-tumor, toxic, and side effect in vivo. Besides, the anti-tumor mechanism of LH-1 was studied by mRNA sequencing. In vitro, LH-1 could inhibit the proliferation and migration of melanoma cells A375 and B16-F10 in a dose-dependent manner and promote tumor cell apoptosis through the mitochondrial apoptosis pathway. In vivo assays confirmed that LH-1 could suppress melanoma growth by inducing cell apoptosis and reducing cell proliferation, and it did not have any notable toxic effects on normal tissues. LH-1 may play an anti-melanoma role by upregulating OBSCN gene expression. These findings suggest that LH-1 may be a potential for the treatment of melanoma.

6.
Front Psychol ; 13: 1012455, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275308

RESUMO

Negative problem orientation (NPO) has become an essential construct for comprehending social problem-solving deficits. However, the heterogeneity of NPO has not yet been explored. With a sample of Chinese adolescents (N = 2,174), four latent profiles were identified as lower NPO, moderate NPO, self-inefficacy and negative outcome expectancy (SI&NOE), and dysfunctional NPO. Compared to the lower NPO and moderate NPO, a greater percentage of boys in the SI&NOE and dysfunctional NPO profiles than were girls. In addition, lower grades and younger adolescents tended to engage in the moderate NPO and SI&NOE profiles. The dysfunctional NPO reported higher levels of worry, depressive symptoms, anxiety, and stress, and worse sleep quality than the other profiles. The implications of these findings are discussed herein.

7.
Anim Nutr ; 11: 102-111, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36189377

RESUMO

Reportedly, proteins involved in lipid metabolism change significantly in the jejunal crypt cells of early-weaned piglets, but the exact lipid profile change remains uncertain. In the present study, 32 piglets weaned at 21 d of age were randomly divided into 4 groups with 8 replicates. The jejunal crypt cells of a group of piglets on the post-weaning day (PWD) 1, 3, 7, and 14 were isolated per time point. Crypt cell lipid profiles were analyzed using ultra-high-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry. This study showed that piglets suffered the greatest weaning stress on PWD 3 in terms of the lowest relative weight of the small intestine, the highest relative weight of the spleen, and the highest levels of malondialdehyde, cholesterol, and low-density lipoprotein cholesterol. The lipid profile of jejunal crypt cells including carnitine, sulfatide, sphingomyelin, hexosylceramide, and ceramide greatly changed after weaning, especially between PWD 3 and 14 (P < 0.05). The differential lipid species between these 2 d were mainly involved in the glycerophospholipid metabolism pathway. In addition, potential lipid biomarkers for weaning stress in crypt cells such as phosphatidylcholine (PC) (9:0/26:1), PC (17:0/18:2), carnitine (24:0), carnitine (22:0), sphingomyelin (d14:1/22:0), PC (P-18:0/18:4), phosphatidylethanolamine (P-16:0/20:4), phosphatidylinositol (15:1/24:4), and dihexosylceramide (d14:1/26:1) were identified. The changes in lipid profile might be related to the inflammation caused by early weaning. These findings might provide new therapeutical targets for intestinal dysfunctions caused by weaning stress.

8.
Clin Cosmet Investig Dermatol ; 15: 2177-2186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267690

RESUMO

Vitiligo is a chronic depigmenting disorder of the skin and mucosa caused by the destruction of epidermal melanocytes. Although the exact mechanism has not been elucidated, studies have shown that oxidative stress plays an important role in the pathogenesis of vitiligo. High mobility group box protein B1 (HMGB1) is a major nonhistone protein and an extracellular proinflammatory or chemotactic molecule that is actively secreted or passively released by necrotic cells. Recent data showed that HMGB1 is overexpressed in both blood and lesional specimens from vitiligo patients. Moreover, oxidative stress triggers the release of HMGB1 from keratinocytes and melanocytes, indicating that HMGB1 may participate in the pathological process of vitiligo. Overall, this review mainly focuses on the role of HMGB1 in the potential mechanisms underlying vitiligo depigmentation under oxidative stress. In this review, we hope to provide new insights into vitiligo pathogenesis and treatment strategies.

9.
Animals (Basel) ; 12(18)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36139183

RESUMO

It is well known that the small intestinal epithelial cells of mammals rapidly undergo differentiation, maturation, and apoptosis. However, few studies have defined the physiological state and gene expression changes of enterocytes along the crypt-villus axis in suckling piglets. In the present study, we obtained the intestinal upper villus epithelial cells (F1) and crypt epithelial cells (F3) of 21-day suckling piglets using the divalent chelation and precipitation technique. The activities of alkaline phosphatase, sucrase, and lactase of F1 were significantly higher (p < 0.05) than those of F3. To explore the differences at the gene transcription level, we compared the global transcriptional profiles of F1 and F3 using RNA-seq analysis technology. A total of 672 differentially expressed genes (DEGs) were identified between F1 and F3, including 224 highly expressed and 448 minimally expressed unigenes. Functional analyses indicated that some DEGs were involved in the transcriptional regulation of nutrient transportation (SLC15A1, SLC5A1, and SLC3A1), cell differentiation (LGR5, HOXA5 and KLF4), cell proliferation (PLK2 and TGFB3), transcriptional regulation (JUN, FOS and ATF3), and signaling transduction (WNT10B and BMP1), suggesting that these genes were related to intestinal epithelial cell maturation and cell renewal. Gene Ontology (GO) enrichment analysis showed that the DEGs were mainly associated with binding, catalytic activity, enzyme regulator activity, and molecular transducer activity. Furthermore, KEGG pathway analysis revealed that the DGEs were categorized into 284 significantly enriched pathways. The greatest number of DEGs enriched in signal transduction, some of which (Wnt, Hippo, TGF-beta, mTOR, PI3K-Akt, and MAPK signaling pathways) were closely related to the differentiation, proliferation, maturation and apoptosis of intestinal epithelial cells. We validated the expression levels of eight DEGs in F1 and F3 using qRT-PCR. The present study revealed temporal and regional changes in mRNA expression between F1 and F3 of suckling piglets, which provides insights into the regulatory mechanisms underlying intestinal epithelial cell renewal and the rapid repair of intestinal mucosal damage.

10.
Zhongguo Zhong Yao Za Zhi ; 47(17): 4551-4559, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36164859

RESUMO

Ischemic stroke is one of the main causes of death and long-term disability worldwide, which seriously affects the quality of life of patients and brings a heavy economic burden to families and society. Epidemiological studies have shown that stroke has become the second leading cause of death and major disabling disease in the world, with the characteristics of high morbidity, high recurrence, and high mortality. Epigenetic mechanism is the molecular process where gene expression and function in each cell are dynamically regulated and interconnected and a biological mechanism that changes genetic performance without changing the DNA sequence, including DNA methylation, histone modifications, and non-coding RNA. However, the research on epigenetics is currently focused on other diseases such as tumors. Recent studies have found that epigenetics has received extensive attention in the past few decades as a key factor involved in the pathophysiological process of ischemic stroke. The present study introduced the mediation of epigenetics in the induction of stroke, summarized the potential drug targets for these mechanisms in the treatment of stroke, and further explored the significance of traditional Chinese medicine(TCM) against cerebral ischemia injury based on TCM classification of stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Metilação de DNA , Epigênese Genética , Humanos , AVC Isquêmico/genética , Qualidade de Vida , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Acidente Vascular Cerebral/genética
11.
Genes Genomics ; 44(11): 1323-1331, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36087248

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) play an essential role in biological processes. However, the expression patterns of lncRNAs that regulate the non-Mendelian inheritance feather phenotypes remain unknown. OBJECTIVE: This study aimed to compare the expression profiles of lncRNAs in the follicles of the late-feathering cocks (LC) and late-feathering hens (LH) that followed genetic rules and the early-feathering hen (EH) and early-feathering cock (EC) that did not conform to the genetic laws. METHODS: We performed RNA sequencing and investigated the differentially expressed lncRNAs (DElncRNAs) between the early- and late-feathering chickens, which function by cis-acting or participate in the competing endogenous RNA (ceRNA) network. RESULTS: A total of 53 upregulated and 43 downregulated lncRNAs were identified in EC vs. LC, and 58 upregulated and 109 downregulated lncRNAs were identified in EH vs. LH. The target mRNAs regulated by lncRNAs in cis were enriched in the pentose phosphate pathway, TGF-ß signaling pathway and Jak-STAT signaling pathway in EC vs. LC and were associated with the TGF-ß signaling pathway, Wnt signaling pathway, p53 signaling pathway and Jak-STAT signaling pathway in EH vs. LH. In addition, the lncRNA-mediated ceRNA regulatory pathways of hair follicle formation were mainly enriched in the TGF-ß signaling pathway, Wnt signaling pathway, melanogenesis, and calcium signaling pathways. The levels of ENSGALG00000047626 were significantly higher in the late-feathering chickens than in the early-feathering chickens, which regulated the expression of SSTR2 by gga-miR-1649-5p. CONCLUSION: This study provides a novel molecular mechanism of lncRNA's response to the feather rate that does not conform to the genetic laws in chickens.


Assuntos
Fenômenos Biológicos , MicroRNAs , RNA Longo não Codificante , Animais , Galinhas/genética , Plumas/metabolismo , Feminino , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Análise de Sequência de RNA , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/genética , Via de Sinalização Wnt
12.
Clin Cosmet Investig Dermatol ; 15: 1997-2001, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172248

RESUMO

Signet-ring cell (SRC) is a histologic type in which cells show unique features under the microscope. We mainly found signet-ring cells (SRCs) in gastrointestinal and breast tumors. Cutaneous metastasis from internal carcinomas was an uncommon presentation. The cases of signet-ring cell carcinoma (SRCC) metastasis to the skin were rarely reported. Cutaneous metastasis indicated a poor prognosis for a patient. Here, we report a female who had huge grape-like nodules arising from gastrointestinal SRCC in her trunk and thigh.

13.
Poult Sci ; 101(11): 102122, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36167016

RESUMO

Studies have shown that prebiotics can affect meat quality; however, the underlying mechanisms remain poorly understood. This study aimed to investigate whether prebiotics affect the flavor of chicken meat via the gut microbiome and metabolome. The gut content was collected from chickens fed with or without prebiotics (galacto-oligosaccharides or xylo-oligosaccharides) and subjected to microbiome and metabolome analyses, whereas transcriptome sequencing was performed using chicken breast. Prebiotic supplementation yielded a slight improvement that was not statistically significant in the growth and production performance of chickens. Moreover, treatment with prebiotics promoted fat synthesis and starch hydrolysis, thus increasing meat flavor by enhancing lipase and α-amylase activity in the blood of broiler chickens. The prebiotics altered the proportions of microbiota in the gut at different levels, especially microbiota in the phyla Bacteroidetes and Firmicutes, such as members of the Alistipes, Bacteroides, and Faecalibacterium genera. Furthermore, the prebiotics altered the content of cecal metabolites related to flavor substances, including 8 types of lysophosphatidylcholine (lysoPC) and 4 types of amino acid. Differentially expressed genes (DEGs) induced by prebiotics were significantly involved in fatty acid accumulation processes, such as lipolysis in adipocytes and the adipocytokine signaling pathway. Changes in gut microbiota were correlated with metabolites, for example, Bacteroidetes and Firmicutes were positively and negatively correlated with lysoPC, respectively. Finally, DEGs interacted with cecal metabolites, especially meat-flavor-related amino acids and their derivatives. The findings of this study integrated and incorporated associations among the gut microbiota, metabolites, and transcriptome, which suggests that prebiotics affect the flavor of chicken meat.


Assuntos
Galinhas , Microbiota , Animais , Galinhas/metabolismo , Transcriptoma , Oligossacarídeos/metabolismo , Metaboloma , Carne/análise , Prebióticos/análise
14.
Technol Cancer Res Treat ; 21: 15330338221118413, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35989682

RESUMO

Over the past few decades, immunotherapy has revolutionized the modern medical oncology field. Chimeric antigen receptor (CAR)-T cell therapy has a promising curative effect in the treatment of hematological malignancies. Anti-CD19 CAR-T cells are the most mature CAR-T cells recently studied and in recent years it has achieved a complete remission rate of approximately 90% in the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Although CAR-T cell therapy has greatly alleviated the disease in patients with leukemia or lymphoma, some of them still relapse after treatment. Therefore, in this article, we discuss the factors that may contribute to disease relapse following CAR-T cell therapy and summarize potential strategies to overcome these obstacles, thus providing the possibility of improving standard treatment regimens.


Assuntos
Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Neoplasias Hematológicas/terapia , Humanos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Recidiva
15.
Front Microbiol ; 13: 942027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966699

RESUMO

Acne vulgaris is a chronic inflammatory skin disease in which the influence of gut microbiota has been implicated but without clarification of mechanisms. Gut microbiota may exert such an influence via metabolites, particularly those of tryptophan. End metabolites of tryptophan activate receptors, including aryl hydrocarbon, G protein-coupled, and pregnane X receptors to stabilize the immune microenvironment and intestinal mucosal homeostasis. Any impact on the pathogenesis of acne vulgaris remains unclear. The current review collates recent advances concerning potential roles of tryptophan metabolism in mediating skin inflammation, follicular sebaceous gland function and intestinal permeability, all of which influence the pathogenesis of acne vulgaris. The aim was to improve understanding of the pathogenesis of acne vulgaris and to expose therapeutic opportunities.

16.
Anim Biotechnol ; : 1-10, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35792779

RESUMO

Granulosa cell (GC) apoptosis is the main trigger of follicular atresia. MicroRNAs (miRNAs) are 18-22 nt RNAs whose function is primarily determined by their extended seed region and are considered to be involved in the biological functions of follicular development, including follicular atresia, folliculogenesis, and oogenesis. MiR-138-5p is known to act on chicken GCs. In this study, we found that miR-138-5p was enriched in reproductive organs, such as the uterus and ovaries. To examine whether miR-138-5p could regulate the biological process of GCs, miR-138-5p was examined by transfection of cells with a mimic or inhibitor of miR-138-5p. Expression levels of caspase-3 and caspase-9 mRNA and protein were markedly increased or decreased after transfection of the mimic or inhibitor, respectively. Furthermore, following miR-138-5p inhibition, SIRT1, one of the target genes of miR-138-5p, was found to increase the mRNA, which is correlated with the increased levels of BCL2 expression, an anti-apoptotic gene in the chicken GCs. These results suggest that miR-138-5p promotes apoptosis in chicken GCs by targeting SIRT1.

17.
ACS Appl Mater Interfaces ; 14(30): 34814-34821, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35876251

RESUMO

An interface modification layer plays an important role in improving the performance of organic solar cells (OSCs). The structure design or doping of electrode interlayer materials can effectively inhibit interfacial carrier recombination and improve ohmic contact between the active layer and the electrodes, which is desirable for realizing high power conversion efficiencies (PCEs). Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has been extensively used as a hole-transport layer (HTL) in OSCs. Here, a modification of PEDOT:PSS is proposed using sulfonated graphene (SG) as a secondary dopant for improving the surface morphology and conductivity. The incorporation of the SG-doped PEDOT:PSS as the HTLs in OSCs leads to the increased charge extraction and shows the best PCEs of 17.48% for PM6:Y6 devices and 18.56% for PM6:L8-BO devices. The significant improvement in device performance suggests that SG-PEDOT:PSS is a promising interfacial layer for efficient charge transport and extraction toward high-efficiency OSCs.

18.
J Hematol Oncol ; 15(1): 88, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799191

RESUMO

Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis. In this study, we evaluated chimeric antigen receptor (CAR) T cell therapy targeting CLL-1 in adults with R/R AML patients. Patients received conditioning chemotherapy with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days and an infusion of a dose of 1-2 × 106 CAR-T cells/kg. The incidence of dose-limiting toxicity was the primary endpoint. Ten patients were treated, and all developed cytokine release syndrome (CRS); 4 cases were low-grade, while the remaining 6 were considered high-grade CRS. No patient developed CAR-T cell-related encephalopathy syndrome (CRES). Severe pancytopenia occurred in all patients. Two patients died of severe infection due to chronic agranulocytosis. The complete response (CR)/CR with incomplete hematologic recovery (CRi) rate was 70% (n = 7/10). The median follow-up time was 173 days (15-488), and 6 patients were alive at the end of the last follow-up. CAR-T cells showed peak expansion within 2 weeks. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML.


Assuntos
Agranulocitose , Leucemia Linfocítica Crônica de Células B , Leucemia Mieloide Aguda , Adulto , Antígenos CD19 , Síndrome da Liberação de Citocina , Humanos , Imunoterapia Adotiva/efeitos adversos , Leucemia Mieloide Aguda/terapia , Linfócitos T
19.
Clin Cosmet Investig Dermatol ; 15: 1225-1236, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800455

RESUMO

Purpose: Taohong Siwu decoction (THSWD) is traditionally used to treat androgenic alopecia (AGA) in clinical practice of traditional Chinese medicine. This study used a network pharmacology approach to elucidate the molecular mechanism governing the effect of THSWD on AGA. Materials and Methods: The major active components and their corresponding targets of THSWD were screened. AGA-related targets were obtained by analyzing the differentially expressed genes between AGA patients and healthy individuals. The protein-protein interaction networks of putative targets of THSWD and AGA-related targets were visualized and merged to identify the candidate targets for THSWD against AGA. Gene ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for core targets were performed. Finally, the key effective components and core targets screened were verified by molecular docking. Results: In this study, 69 compounds and 202 compound targets of THSWD, as well as 1158 disease targets, were screened. Forty-five interactive targets were identified for constructing the "ingredient-targets" network. The functional annotations of target genes were found to be related to oxidative stress, reactive oxygen species, and hydrogen peroxide. Pathways involved in the treatment of AGA included apoptosis and PI3K-AKT signaling pathways. The luteolin, quercetin, kaempferol, baicalein, and beta-carotene were identified as the vital active compounds, and AKT1, TP53, JUN, CASP3 and MYC were considered as the core targets. Assessment of molecular docking revealed that these active compounds and targets had good-binding interactions. Conclusion: The results indicated that the effects of THSWD against AGA may be related to anti-inflammation and anti-oxidation properties of the compounds through the specific biological processes and the related pathways.

20.
Clin Cosmet Investig Dermatol ; 15: 1105-1107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734146

RESUMO

Most patients are anxious about the skin lesions on the penis. This study reports a case of lichen nitidus on the penis and reviews related literature. A 40-year-old male has presented with small papules with skin color on the penis for one year. The patient was diagnosed with lichen nitidus, and tacrolimus cream and humectant were topically administered after diagnosis. The symptoms were alleviated after treatment. We first report a series of the cases with lichen nitidus on the penis, knowing the clinical and pathological manifestations of this disease can reduce misdiagnosis and unnecessary treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...