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1.
Int Immunopharmacol ; 143(Pt 1): 113229, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39357208

ABSTRACT

T-bet and Eomes, both T-box transcription factors, have been extensively studied for their critical roles in the differentiation and functional maintenance of various immune cells. In this review, we provide a focused overview of their contributions to the transcriptional activation and differentiation, development, and terminal maturation of natural killer cells and innate lymphoid cell 1 cells. Furthermore, the interplay between T-bet and Eomes in regulating NK cell function, and its subsequent implications for immune responses against infections and tumors, is thoroughly examined. The review explores the ramifications of dysregulated transcription factor expression, examining its impact on homeostatic balance and its role in a spectrum of disease models. Expression variances among distinct NK cell subsets resident in different tissues are highlighted to underscore the complexity of their biological roles. Collectively, this work aims to expand the current understanding of NK cell biology, thereby paving the way for innovative approaches in the realm of NK cell-based immunotherapies.

2.
Front Oncol ; 14: 1422800, 2024.
Article in English | MEDLINE | ID: mdl-39228990

ABSTRACT

GCA, also known as Buschke-Lowenstein tumor, is a rare sexually transmitted disease associated with HPV types 6 and 111. These warts are considered histologically benign, but there is a risk of localized invasion and development of malignancy. This malignant transformation occurs most often in the perianal and vulvar areas, and involvement of other sites is relatively rare2. In this case, we report a rare case of a giant wart originating from breast skin infected with HPV and progressing to cutaneous squamous cell carcinoma.

3.
Plant Signal Behav ; 19(1): 2399426, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39231270

ABSTRACT

Tripartite interactions among plants, fungi, and bacteria are critical for maintaining plant growth and fitness, and volatile organic compounds (VOCs) play a significant role in these interactions. However, the functions of VOCs within the niche of mycoheterotrophic plants, which represent unique types of interactions, remain poorly understood. Gastrodia elata, a mycoheterotrophic orchid species, forms a symbiotic relationship with specific Armillaria species, serving as a model system to investigate this intriguing issue. Rahnella aceris HPDA25 is a plant growth-promoting bacteria isolated from G. elata, which has been found to facilitate the establishment of G. elata-Armillaria symbiosis. In this study, using the tripartite symbiotic system of G. elata-Armillaria gallica-R. aceris HPDA25, we investigate the role of VOCs in the interaction among mycoheterotrophic plants, fungi, and bacteria. Our results showed that 33 VOCs of HPDA25-inducible symbiotic G. elata elevated compared to non-symbiotic G. elata, indicating that VOCs indeed play a role in the symbiotic process. Among these, 21 VOCs were accessible, and six active VOCs showed complete growth inhibition activities against A. gallica, while R. aceris HPDA25 had no significant effect. In addition, three key genes of G. elata have been identified that may contribute to the increased concentration of six active VOCs. These results revealed for the first time the VOCs profile of G. elata and demonstrated its regulatory role in the tripartite symbiotic system involving G. elata, Armillaria, and bacteria.


Subject(s)
Armillaria , Gastrodia , Symbiosis , Volatile Organic Compounds , Symbiosis/physiology , Volatile Organic Compounds/metabolism , Gastrodia/microbiology , Gastrodia/metabolism , Gastrodia/genetics , Armillaria/metabolism , Armillaria/genetics
4.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4007-4014, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39307735

ABSTRACT

To investigate the influence of the strigolactone inhibitor Tis108 on the growth of Gastrodia elata, this study treated G. elata tuber with Tis108 solution of 10 µmol·L~(-1) and measured the content of endogenous hormone gibberellin(GA) in the tuber. By using reverse transcription-polymerase chain reaction(RT-PCR) technology, the key enzyme GeCYP714A1 gene involved in GA deactivation was cloned. Bioinformatics analysis on the GeCYP714A1 gene was carried out by using ExPASy, SWISS-MODEL, MEGA, etc., and its expression levels in different parts of G. elata were determined. The results showed that after Tis108 treatment, GA content in G. elata tuber was significantly increased, and the transcription level of the GeCYP714A1 gene was significantly decreased. The full length of the coding region of the GeCYP714A1 gene is 1 173 bp, encoding 390 amino acids. The protein has a molecular weight of 44.85 kDa, a theoretical isoelectric point of 9.83, an instability index of 49.20, an aliphatic index of 89.03, and a grand average of hydropathicity of-0.235, classifying it as an unstable, basic, hydrophilic protein, and the GeCYP714A1 protein was localized in the mitochondria, lacking a signal peptide and a transmembrane structure. Phylogenetic tree analysis revealed that GeCYP714A1 was most closely related to the DcCYP714C2(PKU78454.1) protein from Dendrobium candidum, with a sequence identity of 67.25%. The qRT-PCR analysis of the expression patterns of the GeCYP714A1 gene indicated that GeCYP714A1 had the highest transcription level in G. elata tuber, followed by stem and inflorescence. The study represented that Tis108 inhibited the transcription level of GeCYP714A1 involved in GA deactivation in G. elata tuber, thereby increasing the accumulation of GA and affecting the growth of G. elata tuber. These results provided a basis for further studies of strigolactone regulation of GA signal and tuber development in G. elata.


Subject(s)
Gastrodia , Gibberellins , Plant Proteins , Gastrodia/genetics , Gastrodia/chemistry , Gibberellins/pharmacology , Gibberellins/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Gene Expression Regulation, Plant/drug effects , Lactones/pharmacology , Phylogeny , Amino Acid Sequence
5.
Plant Physiol Biochem ; 215: 109027, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39154422

ABSTRACT

ATP-binding cassette (ABC) transporters are vital for plant growth and development as they facilitate the transport of essential molecules. Despite the family's significance, limited information exists about its functional distinctions in Citrus medica. Our study identified 119 genes encoding ABC transporter proteins in the C. medica genome. Through an evolutionary tree and qPCR analysis, two ABC genes, CmABCB19 and CmABCC10, were implicated in C. medica fruit development, showing upregulation in normal fruits compared to malformed fruits. CmABCB19 was found to localize to the plasma membrane of Nicotiana tabacum, exhibiting indole-3-acetic acid (IAA) efflux activity in the yeast mutant strain yap1. CmABCC10, a tonoplast-localized transporter, exhibited efflux of diosmin, nobiletin, and naringin, with rutin influx in strain ycf1. Transgenic expression of CmABCB19 and CmABCC10 in Arabidopsis thaliana induced alterations in auxin and flavonoid content, impacting silique and seed size. This effect was attributed to the modulation of structural genes in the auxin biosynthesis (YUC5/9, CYP79B2, CYP83B1, SUR1) and flavonoid biosynthesis (4CL2/3, CHS, CHI, FLS1/3) pathways. In summary, the functional characterization of CmABCB19 and CmABCC10 illuminates auxin and flavonoid transport, offering insights into their interplay with biosynthetic pathways and providing a foundation for understanding the transporter's role in fruit development.


Subject(s)
ATP-Binding Cassette Transporters , Citrus , Fruit , Plant Proteins , Citrus/genetics , Citrus/metabolism , Citrus/growth & development , Fruit/growth & development , Fruit/genetics , Fruit/metabolism , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Indoleacetic Acids/metabolism , Gene Expression Regulation, Plant , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/growth & development , Plants, Genetically Modified , Flavanones/metabolism , Nicotiana/genetics , Nicotiana/metabolism , Nicotiana/growth & development , Genome-Wide Association Study , Flavonoids/metabolism , Diosmin/metabolism
6.
Int Immunopharmacol ; 141: 112958, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39159564

ABSTRACT

Acute myeloid leukemia (AML) is one of the most common types of blood cancer in adults and is associated with a poor survival rate. NK cells play a crucial role in combating AML, and alterations in immune checkpoint expression can impair NK cell function against AML. Targeting certain checkpoints may restore this function. CD96, an inhibitory immune checkpoint, has unclear expression and roles on NK cells in AML patients. In this study, we initially evaluated CD96 expression and compared CD96+ NK with the inhibitory receptor and stimulatory receptors on NK cells from AML patients at initial diagnosis. We observed increased CD96 expression on NK cells with dysfunctional phenotype. Further analysis revealed that CD96+ NK cells had lower IFN-γ production than CD96- NK cells. Blocking CD96 enhanced the cytotoxicity of primary NK and cord blood-derived NK (CB-NK) cells against leukemia cells. Notably, patients with a high frequency of CD96+ NK cells at initial diagnosis exhibited poorer clinical outcomes. Additionally, TGF-ß1 was found to enhance CD96 expression on NK cells via SMAD3 signaling. These findings suggest that CD96 is invovled in NK dysfunction against AML blast, and might be a potential target for restoring NK cell function in the fight against AML.


Subject(s)
Antigens, CD , Killer Cells, Natural , Leukemia, Myeloid, Acute , Transforming Growth Factor beta1 , Humans , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/diagnosis , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Transforming Growth Factor beta1/metabolism , Antigens, CD/metabolism , Prognosis , Male , Female , Middle Aged , Adult , Aged , Interferon-gamma/metabolism , Smad3 Protein/metabolism , Cell Line, Tumor , Signal Transduction , Cytotoxicity, Immunologic , Young Adult
7.
Adv Med Sci ; 69(2): 303-311, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986767

ABSTRACT

PURPOSE: Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis. METHODS: Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry. RESULTS: IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues. CONCLUSIONS: IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 â€‹cells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management.

8.
Front Immunol ; 15: 1411300, 2024.
Article in English | MEDLINE | ID: mdl-38911868

ABSTRACT

The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field.


Subject(s)
Immunotherapy, Adoptive , Receptors, Chimeric Antigen , T-Lymphocytes , Thyroid Neoplasms , Humans , Thyroid Neoplasms/therapy , Thyroid Neoplasms/immunology , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Animals , T-Lymphocytes/immunology , T-Lymphocytes/transplantation , Clinical Trials as Topic , Treatment Outcome
9.
Arch Dermatol Res ; 316(5): 176, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758283

ABSTRACT

Psoriasis is a chronic immune mediated inflammatory skin disease with systemic manifestations. It has been reported that caloric restriction could improve severity of psoriasis patients. However, the mechanism of intermittent fasting effects on psoriasis has not been investigated. Caloric restriction is known to reduce the number of circulating inflammatory monocytes in a CCL2-dependent manner. However, it is still unknown whether caloric restriction can improve psoriasis by regulating monocytes through CCL2. In this study, we used imiquimod (IMQ)-induced psoriasis-like mouse model to explore the effects and the mechanisms of intermittent fasting on psoriasis-like dermatitis. We found that intermittent fasting could significantly improve IMQ-induced psoriasis-like dermatitis, and reduce the number of γδT17 cells and IL-17 production in draining lymph nodes and psoriatic lesion via inhibiting proliferation and increasing death of γδT17 cells. Furthermore, intermittent fasting could significantly decrease monocytes in blood, and this was associated with decreased monocytes, macrophages and DC in psoriasis-like skin inflammation. Reduced monocytes in circulation and increased monocytes in BM of fasting IMQ-induced psoriasis-like mice is through reducing the production of CCL2 from BM to inhibit monocyte egress to the periphery. Our above data shads light on the mechanisms of intermittent fasting on psoriasis.


Subject(s)
Chemokine CCL2 , Disease Models, Animal , Fasting , Imiquimod , Monocytes , Psoriasis , Animals , Psoriasis/immunology , Psoriasis/chemically induced , Psoriasis/pathology , Monocytes/immunology , Monocytes/metabolism , Mice , Fasting/blood , Chemokine CCL2/metabolism , Th17 Cells/immunology , Interleukin-17/metabolism , Skin/pathology , Skin/immunology , Humans , Mice, Inbred C57BL , Male , Cell Proliferation , Caloric Restriction , Intermittent Fasting
10.
Chemosphere ; 358: 142095, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663681

ABSTRACT

Exposure to indoor dust is of concern since dust may be contaminated by various toxic chemicals and people spend considerable time indoors. Factors impacting human exposure risks to contaminants in indoor dust may differ from those affecting the loadings of contaminants, but the dominant factors have not yet been well clarified. In this study, the occurrence, human exposure, and related influencing factors of several classes of legacy and emerging contaminants in residential dust across Beijing were investigated, including per- and polyfluoroalkyl substances (PFASs) and three types of flame retardants (FRs), i.e., organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), and novel halogenated FRs (NHFRs). OPEs (median: 3847 ng/g) were the most abundant group, followed by PBDEs (1046 ng/g) and NHFRs (520 ng/g). PFASs (14.3 ng/g) were one to two orders of magnitude lower than FRs. The estimated daily intakes of these contaminants were relatively higher for toddlers than other age groups, with oral ingestion being the main exposure pathway compared with dermal contact. Higher human exposure risks were found in new buildings or newly finished homes due to the elevated intake of emerging contaminants (such as OPEs). Furthermore, higher risks were also found in homes with wooden floors, which were mainly associated with higher levels of PFASs, chloroalkyl and alkyl OPEs, compared with tile floors. Citizens in the urban area also showed higher exposure risks than those in the suburban area. The quantity of household appliances and finishing styles (simple or luxurious) showed an insignificant impact on overall human exposure risks despite their significant effect on the levels of some of the dust contaminants. Results in this study are of importance in understanding human exposure to the co-existence of multiple contaminants in indoor dust.


Subject(s)
Air Pollution, Indoor , Dust , Environmental Exposure , Environmental Monitoring , Flame Retardants , Halogenated Diphenyl Ethers , Housing , Dust/analysis , Humans , Air Pollution, Indoor/analysis , Air Pollution, Indoor/statistics & numerical data , Beijing , Flame Retardants/analysis , Environmental Exposure/statistics & numerical data , Environmental Exposure/analysis , Halogenated Diphenyl Ethers/analysis , Child , Adult , Child, Preschool , Air Pollutants/analysis , Organophosphates/analysis , Infant , China , Adolescent
12.
J Sci Food Agric ; 104(9): 5042-5051, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38319685

ABSTRACT

BACKGROUND: The use of synbiotics is emerging as a promising intervention strategy for regulating the gut microbiota and for preventing or reducing obesity, in comparison with the use of probiotics or prebiotics alone. A previous in vivo study revealed that Lacticaseibacillus paracasei K56 (L. paracasei K56) could alleviate obesity induced in high-fat-diet mice; however, the effect of the synbiotic combination of L. paracasei K56 and prebiotics in obese individuals has not been explored fully. RESULTS: The effect of prebiotics on the proliferation of L. paracasei K56 was determined by spectrophotometry. The results showed that polydextrose (PG), xylooligosaccharide (XOS), and galactooligosaccharide (GOS) had a greater potential to be used as substrates for L. paracasei K56 than three other prebiotics (melitose, stachyose, and mannan-oligosaccharide). An in vitro fermentation model based on the feces of ten obese female volunteers was then established. The results revealed that K56_GOS showed a significant increase in GOS degradation rate and short-chain fatty acid (SCFA) content, and a decrease in gas levels, compared with PG, XOS, GOS, K56_PG, and K56_XOS. Changes in these microbial biomarkers, including a significant increase in Bacteroidota, Bifidobacterium, Lactobacillus, Faecalibacterium, and Blautia and a decrease in the Firmicutes/Bacteroidota ratio and Escherichia-Shigella in the K56_GOS group, were associated with increased SCFA content and decreased gas levels. CONCLUSION: This study demonstrates the effect of the synbiotic combination of L. paracasei K56 and GOS on obese individuals and indicates its potential therapeutic role in obesity treatment. © 2024 Society of Chemical Industry.


Subject(s)
Fermentation , Gastrointestinal Microbiome , Lacticaseibacillus paracasei , Obesity , Oligosaccharides , Synbiotics , Humans , Obesity/metabolism , Obesity/microbiology , Obesity/diet therapy , Synbiotics/administration & dosage , Oligosaccharides/metabolism , Oligosaccharides/administration & dosage , Female , Adult , Lacticaseibacillus paracasei/metabolism , Feces/microbiology , Feces/chemistry , Prebiotics/analysis , Probiotics/administration & dosage , Young Adult , Middle Aged
13.
Nat Commun ; 15(1): 227, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38172093

ABSTRACT

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.


Subject(s)
Bifidobacterium animalis , Dyspepsia , Probiotics , Humans , Dyspepsia/therapy , Probiotics/therapeutic use , Feces/microbiology , Double-Blind Method
14.
Transl Res ; 265: 26-35, 2024 03.
Article in English | MEDLINE | ID: mdl-37914149

ABSTRACT

Lynch syndrome, an autosomal dominant hereditary disease arising from mutations in mismatch repair genes, is linked to the development of multiple tumor types, notably colorectal cancer, endometrial carcinoma and upper urinary tract urothelial carcinoma. In this study, we present the case of a young patient diagnosed with upper urinary tract urothelial carcinoma, notable for a familial history of diverse malignancies. By employing genetic analysis, we verified the presence of Lynch syndrome within the family and detected novel variants, MSH2 p.A604D and TSC2 p.C738Y, utilizing NGS technology. Subsequently, we conducted validation experiments to assess the pathogenicity of the MSH2 and TSC2 variants. We illustrated that the MSH2 variant can result in diminished MSH2 expression, compromised mismatch repair function, and induce resistance to cisplatin in urothelial carcinoma. Furthermore, we substantiated the promotional impact of the identified TSC2 variant on urothelial carcinoma, encompassing proliferation, invasion, and migration. Significantly, we found that the MSH2 p.A604D variant and TSC2 p.C738Y variant synergistically enhance the promotion of urothelial carcinoma.


Subject(s)
Carcinoma, Transitional Cell , Colorectal Neoplasms, Hereditary Nonpolyposis , Kidney Neoplasms , Urinary Bladder Neoplasms , Humans , Carcinoma, Transitional Cell/genetics , China , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , MutS Homolog 2 Protein/genetics , Urinary Bladder Neoplasms/genetics
15.
J Ethnopharmacol ; 319(Pt 3): 117309, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37858750

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Coix lacryma-jobi var. ma-yuen (Romanet du Caillaud) Stapf is a plant of the genus Coix in the Gramineae family. Coix seed is cultivated in various regions throughout China. In recent years, with the research on the medicinal value of Coix seed, it has received more and more widespread attention from people. Numerous pharmacological effects of Coix seed have been demonstrated through modern pharmacological studies, such as hypoglycemia, improving liver function, anti-tumor, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. AIMS OF THE STUDY: This article is a literature review. In recent years, despite the extensive research on Coix seed, there has yet to be a comprehensive review of its traditional usage, medicinal resources, chemical components, and pharmacological effects is still lacking. To fill this gap, the paper provides an overview of the latest research progress on Coix seed, aiming to offer guidance and references for its further development and comprehensive utilization. MATERIAL AND METHODS: To gather information on the traditional usage, phytochemical ingredients, and pharmacological properties of Coix seed, we conducted a literature search using both Chinese and English languages in five databases: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Springer. RESULTS: This article is a literature review. The chemical constituents of Coix seed include various fatty acids, esters, polysaccharides, sterols, alkaloids, triterpenes, tocopherols, lactams, lignans, phenols, flavonoids and other constituents. Modern pharmacological research has indeed shown that Coix seed has many pharmacological effects and is a natural anti-tumor drug. In addition to its anti-tumor effect, it also has pharmacological effects such as hypoglycemia, improving liver function, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. CONCLUSIONS: This article provides a brief overview of the traditional uses, biotechnological applications, chemical components, and pharmacological effects of Coix seed. It highlights the importance of establishing quality standards, discovering new active ingredients, and exploring pharmacological mechanisms in Coix seed research. The article also emphasizes the significance of clinical trials, toxicology studies, pharmacokinetics data, and multidisciplinary collaboration for further advancements in this field. Overall, it aims to enhance understanding of Coix seed and its potential in pharmaceutical development and wellness products.


Subject(s)
Coix , Hypoglycemia , Humans , Seeds , Poaceae , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
16.
AAPS PharmSciTech ; 25(1): 7, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38147267

ABSTRACT

Ginkgolides are receptor antagonist of platelet activating factor with great clinical prospect, but its application is limited by its low solubility, short half-life and poor alkaline environment stability. It is difficult to solve these problems with a single drug delivery system. In this study, supersaturated self-nanoemulsifying gastric floating tablets of ginkgolides were developed through the combination of solid supersaturated self-nanoemulsifying drug delivery system (solid S-SNEDDS) and gastric retentive floating drug delivery system (GFDDS) to solve these problems of ginkgolides. Solid S-SNEDDS was prepared by D-optimal mixture design, normalization method and single factor experiment. The properties of solid-S-SNEDDS were studied by TEM, PXRD, FT-IR, SEM and in vitro drug release profile. Then, the optimal formulation of stomach floating tablet was obtained through single factor experiment and center composite design, followed by the study of in vitro release, model and mechanism of release, in vitro buoyancy and kinetics of erosion and swelling. PXRD and FT-IR showed that the drug in solid S-SNEDDS existed in an amorphous manner and formed hydrogen bond with excipients. The results showed that the cumulative release of GA and GB in the optimal tablets was 96.12% and 92.57% higher than the simple tablets within 12 h. The release mechanism of the tablet was skeleton erosion and drug diffusion. In 12 h, the optimal tablets can float stably in vitro and release the drug at a constant rate, with a cumulative release of more than 80%. In summary, the combination of SNEDDS and GFDDS is a promising means to solve the problems of ginkgolides.


Subject(s)
Ginkgolides , Stomach , Delayed-Action Preparations , Spectroscopy, Fourier Transform Infrared , Tablets
17.
Article in English | MEDLINE | ID: mdl-37847626

ABSTRACT

This article aims to solve the optimal tracking problem (OTP) for a class of discrete-time (DT) nonlinear systems with completely unknown dynamics. A novel data-driven deterministic approximate dynamic programming (ADP) algorithm is proposed to solve this kind of problem with only input-output (I/O) data. The proposed algorithm has two advantages compared to existing data-driven deterministic ADP algorithms for the OTP. First, our algorithm can guarantee optimality while achieving better performance in the aspects of time-saving and robustness to data. Second, the near-optimal control policy learned by our algorithm can be implemented without considering expected control and enable the system states to track the user-specified reference signals. Therefore, the tracking performance is guaranteed while simplifying the algorithm implementation. Furthermore, the convergence and stability of the proposed algorithm are strictly proved through theoretical analysis, in which the errors caused by neural networks (NNs) are considered. At the end of this article, the developed algorithm is compared with two representative deterministic ADP algorithms through a numerical example and applied to solve the tracking problem for a two-link robotic manipulator. The simulation results demonstrate the effectiveness and advantages of the developed algorithm.

18.
Int Rev Immunol ; : 1-25, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37882232

ABSTRACT

Regulatory T (Treg) cells are essential for maintaining self-immune tolerance. Reduced numbers or functions of Treg cells have been involved in the pathogenesis of various autoimmune diseases and allograft rejection. Therefore, the approaches that increase the pool or suppressive function of Treg cells in vivo could be a general strategy to treat different autoimmune diseases and allograft rejection. Interleukin-2 (IL-2) is essential for the development, survival, maintenance, and function of Treg cells, constitutively expressing the high-affinity receptor of IL-2 and sensitive response to IL-2 in vivo. And low-dose IL-2 therapy in vivo could restore the imbalance between autoimmune response and self-tolerance toward self-tolerance via promoting Treg cell expansion and inhibiting follicular helper T (Tfh) and IL-17-producing helper T (Th17) cell differentiation. Currently, low-dose IL-2 treatment is receiving extensive attention in autoimmune disease and transplantation treatment. In this review, we summarize the biology of IL-2/IL-2 receptor, the mechanisms of low-dose IL-2 therapy in autoimmune diseases, the application in the progress of different autoimmune diseases, including Systemic Lupus Erythematosus (SLE), Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), Autoimmune Hepatitis (AIH), Alopecia Areata (AA), Immune Thrombocytopenia (ITP) and Chronic graft-versus-host-disease (GVHD). We also discuss the future directions to optimize low-dose IL-2 treatments.


Low-dose interleukin-2 (IL-2) is a potential treatment for autoimmune diseases. IL-2 is a protein that helps regulate the immune system, and low doses of it can activate regulatory T cells (Tregs), which help control the immune response. This can be beneficial in autoimmune diseases where the immune system attacks healthy tissues. We discuss several clinical trials that have investigated the effectiveness of low-dose IL-2 in treating autoimmune diseases. These trials have shown promising results, with some patients experiencing improvements in symptoms and disease progression. However, more research is needed to determine the safety and effectiveness of low-dose IL-2 as a treatment for autoimmune diseases. IL-2 can also activate other immune cells, which may cause unwanted side effects. Therefore, careful monitoring and dosing are necessary when using this treatment. We should also take note of some of the challenges associated with using low-dose IL-2 as a treatment for autoimmune diseases. For example, it can be difficult to determine the optimal dose and dosing schedule for each patient. In addition, there may be individual differences in how patients respond to low-dose IL-2 treatment. Overall, we believe that low-dose IL-2 shows promise as a treatment for autoimmune diseases, but more research is needed to fully understand its potential benefits and risks.

19.
PeerJ ; 11: e16177, 2023.
Article in English | MEDLINE | ID: mdl-37868063

ABSTRACT

Trace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.


Subject(s)
Aconitum , Alkaloids , Microbiota , Trace Elements , Zinc Oxide , Zinc Oxide/pharmacology , Rhizosphere , Zinc , Bacteria , Soil
20.
J Agric Food Chem ; 71(32): 12346-12356, 2023 Aug 16.
Article in English | MEDLINE | ID: mdl-37539957

ABSTRACT

The flavor and taste of Lonicerae japonicae flos (LJF) products are heavily influenced by geographical origin. Tracing the geographical origin is an important aspect of LJF quality assessment. Here, DNA methylation analysis coupled with chemometrics revealed that, in 10 CpG islands upstream of genes in the chlorogenic acid and iridoid biosynthetic pathways, DNA methylation differences appear close association with LJF geographical origin. DNA methylation status in these CpG islands was determined using the cationic conjugated polymer fluorescence resonance energy transfer method. As a result, LJFs from 39 geographical origins were classified into four groups corresponding to Northern China, Central Plain of China, Southeast China, and Western China, according to cluster analysis and principal component analysis. Our findings contribute to an understanding of the modulation of LJF taste and can assist in understanding how DNA methylation in LJF varies with geographical origin.


Subject(s)
DNA Methylation , Fluorescence Resonance Energy Transfer , Cations/chemistry , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Metabolomics , Epigenesis, Genetic , China
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