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1.
Pharmacol Res ; 200: 107072, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38242220

RESUMO

IL-37 is a newly discovered member of the IL-1 cytokine family which plays an important role in regulating inflammation and maintaining physiological homeostasis. IL-37 showed a close relationship with IL-18, another key cytokine in inflammation regulation and cancer development. IL-37 affects the function of IL-18 either by binding to IL-18Rα, a key subunit of both IL-37 and IL-18 receptor, or by drastically neutralizing the IL-18 protein expression of IL-18 binding protein, an important natural inhibitory molecule of IL-18. Moreover, as another subunit receptor of IL-37, IL-1R8 can suppress IL-18Rα expression, functioning as a surveillance mechanism to prevent overactivation of both IL-18 and IL-37 signaling pathways. While IL-18 and IL-37 share the same receptor subunit, IL-18 would in turn interfere with IL-37 signal transduction by binding to IL-18Rα. It is also reported that IL-18 and IL-37 demonstrated opposing effects in a variety of cancers, such as glioblastoma, lung cancer, leukemia, and hepatocellular cancer. Although the mutual regulation of IL-18 and IL-37 and their diametrically opposed effects in cancers has been reported, IL-18 has not been taken into consideration when interpreting clinical findings and conducting mechanism investigations related to IL-37 in cancer. We aim to review the recent progress in IL-18 and IL-37 research in cancer and summarize the correlation between IL-18 and IL-37 in cancer based on their expression level and underlying mechanisms, which would provide new insights into elucidating the conflicting roles of IL-18 and IL-37 in cancer and bring new ideas for translational research related to IL-18 and IL-37.


Assuntos
Interleucina-18 , Neoplasias , Humanos , Interleucina-18/metabolismo , Citocinas , Transdução de Sinais , Inflamação
2.
BMC Musculoskelet Disord ; 25(1): 32, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178051

RESUMO

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common developmental spine disorder among children. It is characterized by a lateral deviation of the spine that gives rise to the distinctive "S" or "C" shaped bending of the spine. The Lin School of Lingnan Region (LSLR), one of the prominent schools for bare-handed orthopaedic manipulation in southern China, provides preliminary evidences that the orthopaedic manipulation techniques help to correct deviations of the spine. Previous research found that Orthopaedic Manipulation Techniques of LSLR (OMT-LSLR) could reduce the Cobb's angles in patients with AIS. Therefore, the current study aims to investigate the effectiveness and safety of the OMT-LSLR in treating teenagers with AIS. METHODS: In this participant-and-assessor-blinded randomized controlled clinical trial, 50 participants identified AIS without surgical indications will be recruited and randomized into two groups to receive physiotherapy scoliosis-specific exercises training with either orthopaedic manipulation or sham manipulation treatment for 16 weeks, followed by post-treatment visits at week 24. Primary outcome measure is the change of Scoliosis Research Society-22 (SRS-22) questionnaire score. Secondary outcome measures include Traditional Chinese version of Spinal Appearance Questionnaire (TC-SAQ) score, Italian Spine Youth Quality of Life (ISYQOL) score, the change of Cobb's angle measured by Xray, and the change of Cobb's angle, spinal rotation and muscle volume measured by three-dimensional (3D) ultrasound. The trial will be conducted at the Chinese University of Hong Kong Chinese Medicine Specialty Clinic cum Clinical Teaching and Research Centre in Hong Kong (CUHK-CMSCTRC). DISCUSSION: The results of this study will establish comprehensive clinical evidence about the efficacy and safety of the Orthopaedic Manipulation Techniques of the Lin School of Lingnan Region in the Treatment of Adolescent Idiopathic Scoliosis. One of the characteristics of this trial is that it is a participant-and-assessor-blinded randomized controlled clinical trial with sham manipulation. The study would also apply three-dimensional (3D) ultrasound technology to investigate the relationship between the change of the muscle volume and the spinal curve. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov (Identifier: NCT05639023 ) on December 6, 2022.


Assuntos
Escoliose , Criança , Humanos , Adolescente , Escoliose/terapia , Escoliose/cirurgia , Manipulação Ortopédica , Qualidade de Vida , Coluna Vertebral , Terapia por Exercício/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39201342

RESUMO

Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Farmacologia em Rede , RNA Ribossômico 16S , Rinite Alérgica , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/microbiologia , Rinite Alérgica/metabolismo , Animais , RNA Ribossômico 16S/genética , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/microbiologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Pyroglyphidae/imunologia , Simulação de Acoplamento Molecular , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Feminino
4.
Molecules ; 29(16)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39202965

RESUMO

Artemisinin is a natural sesquiterpene lactone obtained from the traditional Chinese medicinal herb Artemisia annua L. (qinghao). Artemisinin and its derivatives share an unusual endoperoxide bridge and are extensively used for malaria treatment worldwide. In addition to antimalarial activities, artemisinin and its derivatives have been reported to exhibit promising anticancer effects in recent decades. In this review, we focused on the research progress of artemisinin and its derivatives with potential anticancer activities. The pharmacological effects, potential mechanisms, and clinical trials in cancer therapy of artemisinin and its derivatives were discussed. This review may facilitate the future exploration of artemisinin and its derivatives as effective anticancer agents.


Assuntos
Antineoplásicos , Artemisininas , Artemisininas/química , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Artemisia annua/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico
5.
Cell Biol Toxicol ; 39(1): 319-343, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35701726

RESUMO

Adverse outcome pathways (AOPs) are organized sequences of key events (KEs) that are triggered by a xenobiotic-induced molecular initiating event (MIE) and summit in an adverse outcome (AO) relevant to human or ecological health. The AOP framework causally connects toxicological mechanistic information with apical endpoints for application in regulatory sciences. AOPs are very useful to link endophenotypic, cellular endpoints in vitro to adverse health effects in vivo. In the field of in vitro developmental neurotoxicity (DNT), such cellular endpoints can be assessed using the human "Neurosphere Assay," which depicts different endophenotypes for a broad variety of neurodevelopmental KEs. Combining this model with large-scale transcriptomics, we evaluated DNT hazards of two selected Chinese herbal medicines (CHMs) Lei Gong Teng (LGT) and Tian Ma (TM), and provided further insight into their modes-of-action (MoA). LGT disrupted hNPC migration eliciting an exceptional migration endophenotype. Time-lapse microscopy and intervention studies indicated that LGT disturbs laminin-dependent cell adhesion. TM impaired oligodendrocyte differentiation in human but not rat NPCs and activated a gene expression network related to oxidative stress. The LGT results supported a previously published AOP on radial glia cell adhesion due to interference with integrin-laminin binding, while the results of TM exposure were incorporated into a novel putative, stressor-based AOP. This study demonstrates that the combination of phenotypic and transcriptomic analyses is a powerful tool to elucidate compounds' MoA and incorporate the results into novel or existing AOPs for a better perception of the DNT hazard in a regulatory context.


Assuntos
Rotas de Resultados Adversos , Células-Tronco Neurais , Síndromes Neurotóxicas , Humanos , Ratos , Animais , Laminina/farmacologia , Síndromes Neurotóxicas/etiologia , Estresse Oxidativo , Medição de Risco/métodos
6.
Int J Mol Sci ; 24(11)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37298306

RESUMO

A wound is an interruption of the normal anatomic structure and function of the skin, which is critical in protecting against foreign pathogens, regulating body temperature and water balance. Wound healing is a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, and re-modeling. Factors such as infection, ischemia, and chronic diseases such as diabetes can compromise wound healing, leading to chronic and refractory ulcers. Mesenchymal stem cells (MSCs) have been used to treat various wound models due to their paracrine activity (secretome) and extracellular vehicles (exosomes) that contain several molecules, including long non-coding RNAs (lncRNAs), micro-RNAs (miRNAs), proteins, and lipids. Studies have shown that MSCs-based cell-free therapy using secretome and exosomes has great potential in regenerative medicine compared to MSCs, as there are fewer safety concerns. This review provides an overview of the pathophysiology of cutaneous wounds and the potential of MSCs-based cell-free therapy in each phase of wound healing. It also discusses clinical studies of MSCs-based cell-free therapies.


Assuntos
Transplante de Células-Tronco Mesenquimais , Cicatrização , Cicatrização/fisiologia , Pele , Terapia Baseada em Transplante de Células e Tecidos , Medicina Regenerativa , Reepitelização
7.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674885

RESUMO

Our previous study reported that mesenchymal stem cells (MSCs) accelerated the wound healing process through anti-inflammatory, anti-apoptotic, and pro-angiogenetic effects in a rodent skin excision model. NF3 is a twin-herb formula, which presents similar effects in promoting wound healing. Research focusing on the interaction of MSCs and Chinese medicine is limited. In this study, we applied MSCs and the twin-herb formula to the wound healing model and investigated their interactions. Wound healing was improved in all treatment groups (MSCs only, NF3 only, and MSCs + NF3). The combined therapy further enhanced the effect: more GFP-labelled ADMSCs, collagen I and collagen III expression, Sox9 positive cells, and CD31 positive cells, along with less ED-1 positive cells, were detected; the expressions of proinflammatory cytokine IL-6 and TNF-α were downregulated; and the expression of anti-inflammatory cytokine IL-10 was upregulated. In vitro, NF3 promoted the cell viability and proliferation ability of MSCs, and a higher concentration of protein was detected in the NF3-treated supernatant. A proteomic analysis showed there were 15 and 22 proteins in the supernatants of normal ADMSCs and NF3-treated ADMSCs, respectively. After PCR validation, the expressions of 11 related genes were upregulated. The results of a western blot suggested that the TGFß/Smad and Wnt pathways were related to the therapeutic effects of the combined treatment. Our study suggests for the first time that NF3 enhanced the therapeutic effect of MSCs in the wound healing model and the TGFß/Smad and Wnt pathways were related to the procedure.


Assuntos
Medicamentos de Ervas Chinesas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Medicamentos de Ervas Chinesas/farmacologia , Roedores , Proteômica , Cicatrização , Colágeno/farmacologia , Citocinas/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Anti-Inflamatórios/farmacologia
8.
Molecules ; 28(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37570775

RESUMO

Triple-negative breast cancer (TNBC) is an invasive and persistent subtype of breast cancer that is likely to be resistant to conventional treatments. The rise in immunotherapy has created new modalities to treat cancer, but due to high costs and unreliable efficacy, adjunctive and complementary treatments have sparked interest in enhancing the efficacy of currently available treatments. Natural products, which are bioactive compounds derived from natural sources, have historically been used to treat or ameliorate inflammatory diseases and symptoms. As TNBC patients have shown little to no response to immunotherapy, the potential of natural products as candidates for adjuvant immunotherapy is being explored, as well as their immunomodulatory effects on cancer. Due to the complexity of TNBC and the ever-changing tumor microenvironment, there are challenges in determining the feasibility of using natural products to enhance the efficacy or counteract the toxicity of conventional treatments. In view of technological advances in molecular docking, pharmaceutical networking, and new drug delivery systems, natural products show promise as potential candidates in adjunctive therapy. In this article, we summarize the mechanisms of action of selected natural-product-based bioactive compounds and analyze their roles and applications in combination treatments and immune regulation.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Simulação de Acoplamento Molecular , Imunoterapia , Microambiente Tumoral
9.
Molecules ; 28(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37446658

RESUMO

Vaccination is the most effective method of combating COVID-19 infection, but people with a psychological fear of needles and side effects are hesitant to receive the current vaccination, and alternative delivery methods may help. Bacillus subtilis, a harmless intestinal commensal, has recently earned a strong reputation as a vaccine production host and delivery vector, with advantages such as low cost, safety for human consumption, and straightforward oral administration. In this study, we have succeeded generating "S spores" by engineering B. subtilis with spore coat proteins resembling the spike (S) protein of the ancestral SARS-CoV-2 coronavirus. With the addition of two immunostimulating natural products as adjuvants, namely Astragalus membranaceus (Fisch.) Bge (AM) and Coriolus versicolor (CV), oral administration of S spores could elicit mild immune responses against COVID-19 infection without toxicity. Mucosal IgA against the S protein was enhanced by co-feeding with AM and CV in an S spores-inoculated mouse model. Faster and stronger IgG responses against the S protein were observed when the mice were fed with S spores prior to vaccination with the commercial COVID-19 vaccine CoronaVac. In vitro studies demonstrated that AM, CV, and B. subtilis spores could dose-dependently activate both macrophages and dendritic cells by secreting innate immunity-related IL-1ß, IL-6, and TNF-α, and some other proinflammatory chemokines and cytokines. In conclusion, the combination of S spores with AM and CV may be helpful in developing a vaccine-like supplement against respiratory infection.


Assuntos
Produtos Biológicos , COVID-19 , Vacinas , Humanos , Camundongos , Animais , Vacinas contra COVID-19 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Produtos Biológicos/metabolismo , Esporos Bacterianos/metabolismo , COVID-19/prevenção & controle , COVID-19/metabolismo , SARS-CoV-2 , Imunidade Inata
10.
Cytometry A ; 101(5): 411-422, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34747115

RESUMO

Neurosphere cultures consisting of primary human neural stem/progenitor cells (hNPC) are used for studying the effects of substances on early neurodevelopmental processes in vitro. Differentiating hNPCs migrate and differentiate into radial glia, neurons, astrocytes, and oligodendrocytes upon plating on a suitable extracellular matrix and thus model processes of early neural development. In order to characterize alterations in hNPC development, it is thus an essential task to reliably identify the cell type of each migrated cell in the migration area of a neurosphere. To this end, we introduce and validate a deep learning approach for identifying and quantifying cell types in microscopic images of differentiated hNPC. As we demonstrate, our approach performs with high accuracy and is robust against typical potential confounders. We demonstrate that our deep learning approach reproduces the dose responses of well-established developmental neurotoxic compounds and controls, indicating its potential in medium or high throughput in vitro screening studies. Hence, our approach can be used for studying compound effects on neural differentiation processes in an automated and unbiased process.


Assuntos
Células-Tronco Neurais , Neurônios , Diferenciação Celular/fisiologia , Células Cultivadas , Neurogênese , Neurônios/fisiologia , Organoides
11.
Pharmacol Res ; 175: 106031, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896542

RESUMO

Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. Obesity has been proven to be closely related to colorectal carcinogenesis. This review summarized the potential underlying mechanisms linking obesity to CRC in different aspects, including energy metabolism, inflammation, activities of adipokines and hormones. Furthermore, the potential therapeutic targets of obesity-associated CRC were predicted using network-based target analysis, with total predicted pathways not only containing previously reported pathways, but also putative signaling pathways pending for investigation. In addition, the current conventional therapeutic treatment options, plus the potential use of herbs and natural products in the management of obesity-associated CRC were also discussed. Taken together, the aim of this review article is to provide strong theoretical basis for future drug development, particularly herbs and natural products, in obesity-associated CRC.


Assuntos
Produtos Biológicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Obesidade/tratamento farmacológico , Fitoterapia , Animais , Neoplasias Colorretais/etiologia , Humanos , Obesidade/complicações
12.
Pharmacol Res ; 184: 106457, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36116708

RESUMO

Despite significant advances in the diagnosis and treatment of colorectal cancer (CRC), metastatic colorectal cancer still poses serious threat to CRC patients. The natural gallotannin 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG) has been shown to possess anti-tumor effects on colon cancer cells, but its anti-metastatic effect is yet to be investigated. In this study, the effects of PGG on cell proliferation, colony formation ability, motility, migration were investigated in colon cancer cells using BrdU, colony formation, scratch, and transwell assays, respectively. Western blot assay was used for assessing protein expression. The orthotopic colon tumor-bearing mouse model and human colon cancer metastatic mouse model were employed to evaluate the anti-metastatic effects of PGG. Results showed that PGG exhibited not only anti-proliferative and colony formation inhibitory effects, but also inhibition on cell adhesion, motility, and migration in both HCT116 and colon 26-M01 cells via modulating protein expression of cathepsin B, FAK, cofilin, and epithelial-to-mesenchymal transition related proteins. In addition, PGG (10 or 15 mg/kg, i.p.) could significantly inhibit liver and lung metastasis in colon cancer metastatic mice models. Furthermore, PGG could regulate the populations of T cells, macrophages, and MDSCs, while the levels of IL-2, IL-6, IL-10, IFN-γ, and TNF-α were altered after PGG treatment in metastatic CRC mice. This is the first report of the anti-metastatic effects of PGG by regulating cathepsin B-mediated extracellular matrix dynamics and epithelial-to-mesenchymal transition process in CRC. Our findings suggested that PGG has great potential to be developed as an anti-metastatic agent for metastatic CRC.


Assuntos
Neoplasias do Colo , Taninos Hidrolisáveis , Fatores de Despolimerização de Actina , Animais , Bromodesoxiuridina , Catepsina B , Linhagem Celular Tumoral , Matriz Extracelular , Glucose , Humanos , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/uso terapêutico , Interleucina-10 , Interleucina-2 , Interleucina-6 , Camundongos , Fator de Necrose Tumoral alfa
13.
Inflamm Res ; 71(10-11): 1261-1270, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35916930

RESUMO

OBJECTIVES: We employed the co-culture of CD34+ stem cell-derived human mast cells (HMC) and human monocyte-derived osteoclast precursors to evaluate if mast cells contribute to the pathogenesis of osteoporosis through regulation of osteoclast proliferation and activation. METHODS: Mature HMC and osteoclast precursors were cultured from monocytes isolated from human buffy coat. The osteoclast precursors were incubated with HMC or receptor activator of nuclear factor kappa-B ligand (RANKL) for a week prior to determination of osteoclast maturation through characterization by their morphology and tartrate resistant acid phosphatase (TRAP) expression. The bone absorption activity was determined by pit formation on osteo-assay plate. RESULTS: Mature osteoclasts were identified following co-culture of osteoclast precursors with HMC for one week in the absence of RANKL and they were capable of bone resorption. These actions of HMC on osteoclasts were not affected by mast cell activators such anti-IgE or substance P but could be reversed by osteoprotegerin (OPG) in the co-culture system suggesting the involvement of RANKL. The expression of RANKL on the cell surface of HMC was confirmed by flow cytometry and the density was not affected by activation of HMC. CONCLUSION: Our study provided direct evidence confirming the initiation of osteoclast proliferation and activation by mast cells through cell surface RANKL suggesting that mast cells may contribute to bone destruction in pathological conditions such as osteoporosis.


Assuntos
Mastócitos , Osteoporose , Humanos , Diferenciação Celular , Células Cultivadas , Mastócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Osteoclastos , Osteogênese , Osteoporose/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo
14.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232498

RESUMO

Dry eye is one of the most common ocular surface diseases caused by tear film instability and ocular surface damage due to an abnormal quality or quantity of tears. Inflammatory factors can initiate relevant transduction signalling pathways and trigger the inflammatory cascade response, resulting in ocular surface inflammation. It has been shown that the active ingredients in Dendrobium, such as polysaccharides, alkaloids and phenols, have anti-inflammatory, anti-tumour and immunity-boosting effects, and Dendrobium officinale extract can improve glandular secretion function, increase salivary secretion and increase the expression level of water channel protein in salivary glands in patients with dry eye syndromes. We investigated the in vitro cytoprotective effect of Dendrobium extracts in sodium chloride induced hyperosmotic conditions in human cornea keratocytes (HKs). Results showed that Dendrobium officinale Kimura et Migo water extract (DOW) and Dendrobium loddigesii Rolfe water extract (DLW) could upregulate the expression of aquaporins (AQP)5 protein, thus exerting a repairing effect by promoting cell migration. Furthermore, oral administration of DOW and DLW enhanced tear production in rats and exerted a protective effect on ocular surface damage. DOW and DLW could upregulate the expression of AQP5 and mucin (muc)5ac proteins in the lacrimal gland and reduce the inflammatory response. DOW and DLW inhibited the activation of the corresponding mitogen-activated protein kinases (MAPK) and NF-KB pathway, thereby playing a role in improving dry eye symptoms. This study provides a new perspective on dry eye treatment, and DOW and DLW may be potential therapeutic agents for dry eye.


Assuntos
Dendrobium , Síndromes do Olho Seco , Animais , Anti-Inflamatórios/uso terapêutico , Aquaporina 5/metabolismo , Dendrobium/metabolismo , Síndromes do Olho Seco/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mucinas/metabolismo , NF-kappa B/metabolismo , Fenóis/metabolismo , Polissacarídeos/metabolismo , Ratos , Cloreto de Sódio/metabolismo , Lágrimas/metabolismo , Água/metabolismo
15.
Phytother Res ; 35(4): 2108-2118, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33205491

RESUMO

The biological activities of water-soluble components of edible mushroom Rubinoboletus ballouii (RB) were seldom reported. Polysaccharides of RB (RBP) were prepared and well-characterized using chemical analyses. The immunomodulatory properties of RBP were investigated using human monocyte-derived dendritic cells (moDC) in vitro, and cyclophosphamide (CTX)-induced immunosuppressive mouse model. Results showed that RBP was found to contain 80.6% (w/w) of neutral sugars including D-fucose, D-mannose, D-glucose and D-galactose (1.7:1.4:1.0:1.8), and 12.5% (w/w) of proteins, which composed of glutamine, threonine, serine, etc. RBP could promote the maturation of moDC and increase the secretion of IL-12p40, IL-10, and TNF-α. Furthermore, the stimulation of IL-12p40 production was inhibited by pretreatment with toll-like receptor (TLR)-4 blocker or NF-κB pathway blocker, suggesting that the activation of moDC by RBP was mediated through NF-κB pathway via TLR-4 receptor. On the other hand, in CTX-treated mice, RBP restored the loss of CD34bright CD45dim hematopoietic stem cells and increased IL-2 production in sera and splenocytes culture supernatant, as well as up-regulated the percentage of CD4+ T helper lymphocyte in mice splenocytes. These findings strongly suggested that RBP are the active ingredients of RB responsible for its immunostimulatory actions and deserved to be further investigated as cancer supplements.


Assuntos
Basidiomycota/química , NF-kappa B/metabolismo , Polissacarídeos/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Animais , Humanos , Camundongos , Polissacarídeos/farmacologia
16.
Molecules ; 26(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918834

RESUMO

The immune modulating effects of selected herbs deserve careful studies to gain evidence-based support for their further development. We have been working hard on many items of medicinal herbs to gain insight into their immunomodulatory effects relevant to cancer treatment in particular, while infection control is not excluded. Nine of them have been selected to give the results of our exploration on their biological, particularly immunomodulatory activities. Since Hong Kong people especially favor one medicinal mushroom, viz. Coriolus versicolor, a number of clinical trials using Coriolus for cancer-related studies are included in this review. While immune modulation platforms are being built for relevant studies, a brief account on the research targets and related procedures are given.


Assuntos
Agaricales/química , Antineoplásicos/farmacologia , Fatores Imunológicos/farmacologia , Plantas Medicinais/química , Antineoplásicos/uso terapêutico , Hong Kong , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia
17.
Molecules ; 26(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641576

RESUMO

Herba Patriniae (HP) are medicinal plants commonly used in colorectal cancer (CRC) patients. In this study, network pharmacology was used to predict the active components and key signaling pathways of HP in CRC. Patrinia heterophylla, one type of HP, was chosen for validation of the network pharmacology analysis. The phytochemical profile of Patrinia heterophylla water extract (PHW) was determined by UHPLC-MS. MTT, RT-PCR, and Western blot assays were performed to evaluate the bioactivities of PHW in colon cancer cells. Results showed that 15 potentially active components of HP interacted with 28 putative targets of CRC in the compound-target network, of which asperglaucide had the highest degree. Furthermore, the ErbB signaling pathway was identified as the pathway mediated by HP with the most potential against CRC. Both RT-PCR and Western blot results showed that PHW significantly downregulated the mRNA and protein levels of EGFR, PI3K, and AKT in HCT116 cells. Asperglaucide, present in PHW, exhibited an anti-migratory effect in HCT116 cells, suggesting that it could be an active component of PHW in CRC treatment. In conclusion, this study has provided the first scientific evidence to support the use of PHW in CRC and paved the way for further research into the underlying mechanisms of PHW against CRC.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Dipeptídeos/farmacologia , Descoberta de Drogas/métodos , Receptores ErbB/metabolismo , Proteína Forkhead Box O1/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Medicina Tradicional Chinesa , Patrinia/química , Plantas Medicinais/química
18.
Molecules ; 27(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35011470

RESUMO

Allergic rhinitis (AR) is a highly prevalent allergic disease induced by immunoglobulin (Ig) E-mediated hypersensitivity reaction at the nasal epithelium against inhaled allergens. Previous studies have demonstrated that Pentaherbs formula (PHF), a modified herbal formula comprising five herbal medicines (Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis), could suppress various immune effector cells to exert anti-inflammatory and anti-allergic effects in allergic asthma and atopic dermatitis. The present study aimed to further determine the anti-inflammatory activities of PHF in an ovalbumin (OVA)-induced AR BALB/c mouse model. Nasal symptoms such as sneezing and nose rubbing were recorded and the serum total IgE and OVA-specific IgG1, as well as interleukin (IL)-4, IL-5, IL-10, IL-13, chemokines CXCL9 CXCL10, and tumor necrosis factor (TNF)-α concentrations in nasal lavage fluid (NALF) were measured during different treatments. Effects of PHF on the expression of inflammatory mediators in the sinonasal mucosa were quantified using real-time QPCR. PHF was found to suppress allergic symptoms, infiltration of inflammatory cells, and hyperplasia of goblet cells in the nasal epithelium of the OVA-induced AR mice. PHF could reduce OVA-specific IgG1 level in serum, and TNF-α and IL-10 in nasal lavage fluid (NALF), significantly up-regulate the splenic regulatory T (Treg) cell level, increase the Type 1 helper T cell (Th1)/Type 2 helper T cell (Th2) ratio, and reduce the Th17 cells (all p < 0.05). PHF could also alleviate in situ inflammation in sinonasal mucosa of OVA-induced AR mice. In conclusion, oral treatment of PHF showed immuno-modulatory activities in the OVA-induced AR mice by regulating the splenic T cell population to suppress the nasal allergy symptoms and modulating inflammatory mediators, implicating that PHF could be a therapeutic strategy for allergic rhinitis.


Assuntos
Anti-Inflamatórios/farmacologia , Fatores Imunológicos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Alérgenos/imunologia , Animais , Anti-Inflamatórios/química , Citocinas/metabolismo , Modelos Animais de Doenças , Medicina Herbária , Fatores Imunológicos/química , Imunomodulação/efeitos dos fármacos , Camundongos , Líquido da Lavagem Nasal/imunologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Ovalbumina/administração & dosagem , Extratos Vegetais/química , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/etiologia , Rinite Alérgica/patologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo
19.
J Pak Med Assoc ; 70(1): 35-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31954020

RESUMO

OBJECTIVE: To evaluate the cytotoxicity of crude aqueous and ethanol extracts of Zaleya pentandra against oestrogen receptor-positive breast cancer cell line Michigan Cancer Foundation-7. METHODS: The study was conducted at the Institute of Chinese Medicine, the Chinese University of Hong Kong, Hong Kong, from March to September 2017, and comprised Zaleya pentandra herbaceous perennial plant collected from Pakistani cities of Shakargarh, Lahore and Sialkot. Both aqueous and ethanol extracts were prepared in solvents following Soxhlet extraction technique. Rate of reduction in viability of cancer cell line was studied through MTT (dye compound 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assay on the basis of time of incubation and the dose of extract. Analysis was performed using High Performance Liquid Chromatography with Diode Array Detector in order to found the compounds responsible for the death of cancer cells. RESULTS: Cell viability was observed to be dose-dependent (range: 16.7-37.4%) for aqueous extracts. Minimum inhibition concentration was 16.65% at 200µg/ml after 24 hours of incubation, whereas maximum inhibition was 37.39% at 3200µg/ml. Ethanol extracts showed less inhibition, with maximum inhibition being 25.29% at 1000µg/ml and minimum 13.57% at 62.5µg/ml. Certain polar compounds, like Hydroxytrosol and Tyrosol, could be obtained from the aqueous extracts only. CONCLUSIONS: Zaleya pentandra aqueous extract was found to have potential benefit towards cytotoxicity of breast cancer cells.


Assuntos
Aizoaceae , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Extratos Vegetais/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Células MCF-7 , Extratos Vegetais/química
20.
J Clin Densitom ; 22(3): 409-419, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29307693

RESUMO

This study aims to evaluate endplate/cortex fracture (ECF)-based method for detecting osteoporotic vertebral fracture (VF) in elderly Chinese population (age ≥ 65 years). The radiographs of 1954 elderly Chinese men (mean: 72.3 years) and 1953 elderly Chinese women (mean: 72.5 years) were evaluated according to Genant's morphometrical vertebral deformity (VD) severity criteria, as well as identified VF according to ECF without necessary requirement of VD. According to ECF, grade-1, -2, and -3 VF prevalence was 1.89%, 1.74%, and 2.25% in men, and 3.33%, 3.07%, and 5.89% in women, respectively. In men and women, 15.7% (35 of 223) and 34.5% (48 of 139) of vertebrae with VD grade-1 deformity were ECF(+, with fracture), respectively. In men and women, 89.7% (35 of 39) and 66.7% (48 of 72) of vertebrae with ECF grade-1 fracture had VD grade-1 deformity. For grade-1 change, ECF(+) subjects tended to have a lower BMD than the VD(+) subjects. In subjects with VD grade-2 deformity, those who were also EC (+) tended to have a lower BMD than those were ECF(-). In all grades, VD(-) and ECF(-) subjects tended to have highest BMD, whereas VD(+) and ECF(+) subjects tended to have lowest BMD. ECF may be more specific for assessing mild VF than the criteria based on vertebral deformity.


Assuntos
Algoritmos , Vértebras Lombares/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , China/epidemiologia , Feminino , Hong Kong/epidemiologia , Humanos , Vértebras Lombares/lesões , Masculino , Fraturas por Osteoporose/epidemiologia , Prevalência , Radiografia , Fraturas da Coluna Vertebral/epidemiologia
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