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1.
J Ethnopharmacol ; 326: 117873, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38346523

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried roots of Rheum palmatum L. and Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) were isolated and extracted from rhubarb. Previous studies have revealed that the early administration of FTRAs protects the intestinal mucosal barrier in rats with severe acute pancreatitis (SAP), the mechanism of which is not yet clear. However, we observed an enhanced expression of intestinal pyroptotic factors in rats treated with SAP, which may be related to the mechanism of intestinal barrier protection by FTRAs. AIM OF THE STUDY: The main objective of this study was to investigate the mechanism by which FTRAs protect the intestinal mucosal barrier in SAP rats, focusing on the classical pyroptosis pathway. MATERIALS AND METHODS: SAP was induced in rats through retrograde injection of sodium taurocholate via the pancreaticobiliary duct. Subsequently, FTRAs (22.5, 45, and 90 mg/kg), rhubarb (900 mg/kg, positive control), and saline (control) were administered at 0 h (immediately), 12 h, and 24 h post-surgery. Pancreatic and intestinal tissue injury, positive PI staining rate, and expression levels of various factors in intestinal tissues were compared across different groups. These factors include diamine oxidase (DAO), lactate dehydrogenase (LDH), high mobility group box chromosomal protein 1(HMGB1) and pro-inflammatory factors in intestinal and serum, pyroptosis-associated factors, toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-kB), apoptosis-associated speck-like protein (ASC), NOD-like receptor protein 3 (NLRP3), cysteine protease-1 (caspase-1) and Gasdermin (GSDMD). RESULTS: The findings indicated that FTRAs protected the damaged intestine and pancreas and restored the expression of intestinal epithelial junction proteins in SAP rats. Additionally, it reduced intestinal and serum levels of DAO, interleukin 1, interleukin 18, HMGB1, and LDH, attenuated intestinal Positive PI staining rate, and significantly decreased the expressions of TLR-4, NF-kB, ASC, NLRP3, caspase-1 and GSDMD in SAP rats. CONCLUSIONS: The results suggest that FTRAs inhibited pyroptosis through down-regulation of the NLRP3-Caspase-1-GSDMD and TLR-4- NF-kB signaling pathways of intestinal tissues., thereby protecting the intestinal barrier of SAP rats.


Assuntos
Proteína HMGB1 , Pancreatite , Rheum , Ratos , Animais , Pancreatite/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Caspase 1 , Ratos Sprague-Dawley , Doença Aguda , Proteínas NLR , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico
2.
Oncol Lett ; 27(2): 49, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38192656

RESUMO

Primary small bowel adenocarcinoma (SBA) is a rare gastrointestinal cancer with a low incidence of ovarian metastasis. Differential diagnosis of metastatic and primary ovarian cancer is often challenging. The present study reported the case of a 45-year-old woman with jejunal adenocarcinoma who presented with right ovarian, left ovarian, abdominopelvic implant and local recurrent bowel wall metastases successively after primary tumor resection. The ovarian masses of the patient originated from SBA, which was confirmed by immunohistochemical results. Following four comprehensive evaluations by an experienced multidisciplinary team (MDT) during the disease period, the patient underwent four operations, 28 cycles of chemotherapy, 24 cycles of targeted therapy and maintenance therapy for 8 months. As of February 2023, the patient has survived for 73 months and has a high quality of life. It is suggested that when a patient with SBA presents with an ovarian mass, the differential diagnosis between metastatic ovarian cancer and primary ovarian cancer mainly relies on immunohistochemistry. After a comprehensive evaluation by an experienced MDT, surgical resection is the primary treatment for advanced SBA, thus demonstrating some benefits for patients.

3.
Future Oncol ; 19(21): 1485-1494, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37466013

RESUMO

Background: To evaluate the safety and efficacy of left colic artery (LCA) preservation in laparoscopic anterior resection with D3 lymphadenectomy for lower rectal cancer. Methods: A total of 117 patients with lower rectal cancer who received laparoscopic anterior resection were retrospectively analyzed. Results: No differences were detected in terms of the numbers of harvested lymph nodes and metastatic lymph nodes, the intraoperative and postoperative complications or the postoperative recurrence and survival rates between the two groups (p > 0.05), but the LCA preservation group showed a lower anastomotic leakage rate than the LCA nonpreservation group (2/49 vs 12/68). Conclusion: LCA preservation may help reduce the incidence of anastomotic leakage without impairing surgical and oncological outcomes.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Artéria Mesentérica Inferior/cirurgia , Estudos Retrospectivos , Neoplasias Retais/patologia , Excisão de Linfonodo/efeitos adversos , Laparoscopia/efeitos adversos
4.
J Ethnopharmacol ; 308: 116266, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36806482

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of anti-inflammation and immunological modulation. The timing of immune regulation is a major problem in the immunotherapy for severe acute pancreatitis (SAP). several studies reported that FTRAs could reduce systemic inflammatory responses by inhibiting early immune overactivity in the gut in rats with SAP. But, the optimal timing of rhubarb and FTRAs administration is not clear in clinical practice. Therefore, the time window for the best efficacy of rhubarb and FTRAs in the treatment of SAP patients should be further elucidated. AIM OF THE STUDY: The main purpose of the present study was to evaluate the efficacy and optimal timing of immune modulation with FTRAs in the treatment of SAP in rats. MATERIALS AND METHODS: FTRAs (22.5, 45 and 90 mg/kg), Rhubarb (RHU) (900 mg/kg, positive control) or normal saline (vehicle control) were initiated at 0 (immediately), 48 and 72 h every 12 h for three times in total. The therapeutic effects of FTRAs and RHU on pancreas and intestinal tissues injury, secondary infection with pseudomonas aeruginosa (PA), amylase, lipase, D-lactic acid (DLA), endotoxin (ET), proinflammatory and anti-inflammatory cytokines, macrophages, dendritic cells and regulatory T cells (Tregs) in the blood, small intestine and/or mesenteric lymph node (MLN) were determined in rats with SAP after treatment. RESULTS: The results showed that administration of FTRAs at 0 h was superior to 48 h and 72 h, which significantly protected the injury of pancreas and intestinal tissues, reduced the mortality induced by secondary infection with PA, decreased the levels of amylase, lipase, DLA, ET, tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-6, IL-8, IL-18 and Tregs, and increased the levels of IL-4, sTNF-αR, macrophages and dendritic cells, secretary immunoglobulin A (SIgA) in the blood and/or small intestinal tissues in rats with SAP. CONCLUSIONS: In conclusion, our studies indicate that the treatment window of FTRAs for SAP is within 48 h of development, administration of FTRAs at the early stage (0 h, immune overreaction period) was the optimal time and superior to that of 48 h and 72 h for its therapeutic efficacy. The earlier the administration of FTRAs, the better the therapeutic efficacy. Therefore, our data may provide a scientific rationale for the clinical application and optimal timing of FTRAs in the treatment of SAP.


Assuntos
Coinfecção , Pancreatite , Rheum , Animais , Ratos , Doença Aguda , Amilases/metabolismo , Antraquinonas/uso terapêutico , Lipase , Pancreatite/tratamento farmacológico , Fator de Necrose Tumoral alfa
6.
Front Oncol ; 12: 1030825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387249

RESUMO

Background: HOXA cluster antisense RNA 2 (lncRNA HOXA-AS2) is a long noncoding RNA (lncRNA) that aberrantly expressed in various cancers and is closely associated with cancer progression. To overcome the limitation of small sample sizes that are inherent to single studies, a meta-analysis was conducted to explore the relationship between the expression level of HOXA-AS2 and cancer prognosis. Methods: Correlational studies were retrieved by searching the databases of PubMed, Embase and Web of Science (up to August 10, 2022). The survival and prognosis data included overall survival (OS), and clinical parameters were gathered and analyzed. Results: Eighteen publications with 1181 patients who were diagnosed with solid tumors were ultimately included. The results showed that, compared with patients with low HOXA-AS2 expression, patients with high HOXA-AS2 expression tended to have poorer overall survival (OS) (HR= 2.52, 95% CI 1.87-3.38, P < 0.01) and shorter disease-free survival (DFS) (HR=7.19, 95% CI 3.20-16.17, P < 0.01). In addition, elevated HOXA-AS2 expression indicated a larger tumor size (OR =2.43, 95% CI 1.53-3.88,P < 0.01), more advanced TNM stage (OR=3.85, 95% CI 2.79-5.31, P < 0.01), earlier lymph node metastasis (LNM) (OR = 4.41, 95% CI 3.05-6.39, P < 0.01) and distant metastasis (DM) (OR= 2.96, 95% CI 1.87-4.7, P < 0.01). Furthermore, HOXA-AS2 expression was notassociated with age (OR=1.15, 95% CI 0.90-1.47), gender (OR=1.16, 95% CI 0.89-1.53), or tumor differentiation (OR=1.21, 95% CI 0.56-2.63). Moreover, aberrant HOXA-AS2 expression was related to drug sensitivity in various types of cancers. Conclusion: The overexpression of HOXA-AS2 predicted poor cancer prognosis in the Chinese population, including poor OS, DFS, TNM, LNM, and DM. HOXA-AS2 could serve as a promising prognostic biomarker and therapeutic target. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022352604.

7.
Front Immunol ; 13: 876168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663952

RESUMO

Background: Immune dysfunction is the main characteristic of severe acute pancreatitis (SAP), and the timing of immune regulation has become a major challenge for SAP treatment. Previous reports about the time point at which the immune status of SAP changed from excessive inflammatory response to immunosuppression (hypo-inflammatory response) are conflicting. Purposes: The aims of this study are to explore the immunological dynamic changes in SAP rats from the perspective of intestinal mucosal immune function, and to determine the immunoswitching point from excessive inflammatory response to immunosuppression. Methods: Retrograde injection of sodium taurocholate into the pancreaticobiliary duct was applied to establish a SAP model in rats. The survival rate and the activities of serum amylase and pancreatic lipase in SAP rats were measured at different time points after model construction. The pathological changes in the pancreas and small intestines were analyzed, and the levels of intestinal pro- and anti-inflammatory cytokines and the numbers of intestinal macrophages, dendritic cells, Th1, Th2, and T regulatory cells were assessed. Meanwhile, the SAP rats were challenged with Pseudomonas aeruginosa (PA) strains to simulate a second hit, and the levels of intestinal inflammatory cytokines and the numbers of immune cells were analyzed to confirm the immunoswitching point. Results: The time periods of 12-24 h and 48-72 h were the two death peaks in SAP rats. The pancreas of SAP rats showed self-limiting pathological changes, and the switching period of intestinal cytokines, and innate and adaptive immunity indexes occurred at 24-48 h. It was further confirmed that 48 h after SAP model construction was the immunoswitching point from excessive inflammatory response to immunosuppression. Conclusion: The SAP rats showed characteristics of intestinal mucosal immune dysfunction after model construction, and the 48th h was identified as the immunoswitching point from excessive inflammatory response to immunosuppression. The results are of great significance for optimizing the timing of SAP immune regulation.


Assuntos
Pancreatite , Doença Aguda , Animais , Citocinas , Pâncreas/patologia , Pancreatite/patologia , Ratos , Ácido Taurocólico
9.
Front Oncol ; 11: 710814, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540677

RESUMO

BACKGROUND: Complete omentectomy is considered to be essential in the radical gastrectomy for gastric cancer (GC), but its clinical benefit remains unclear. This study aims to evaluate the efficacy of omentum-preserving gastrectomy (OPG) for patients with GC. METHODS: Studies comparing the surgical and oncological outcomes of OPG and gastrectomy with complete omentectomy (GCO) for GC up to March 2021 were systematically searched from PubMed, Web of Science, Embase, and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, surgical and oncological outcomes. The RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted. RESULTS: Nine studies with a total of 3335 patients (1372 in the OPG group and 1963 in the GCO group) undergoing gastrectomy were included. In the pooled analysis, the baseline data in two groups were all comparable (p > 0.05). However, the OPG group was associated with shorter operative time (MD = -18.67, 95% CI = -31.42 to -5.91, P = 0.004) and less intraoperative blood loss (MD = -38.09, 95% CI = -53.78 to -22.41, P < 0.00001) than the GCO group. However, the number of dissected lymph nodes (MD = 2.16, 95% CI = -0.61 to 4.93, P = 0.13), postoperative complications (OR = 0.92, 95% CI = 0.74 to 1.15, p = 0.47), overall recurrence rate (OR = 0.83, 95% CI = 0.66 to 1.06, p = 0.14), peritoneal recurrence rate (OR = 0.91, 95% CI = 0.65 to 1.29, p = 0.60), 3-year relapse-free survival (RFS) rate (OR = 1.40, 95% CI = 0.86 to 2.27, p = 0.18), and 5-year RFS rate (OR = 1.21, 95% CI = 0.95 to 1.55, p = 0.12) of the two groups were comparable. CONCLUSIONS: OPG might be an oncologically safe procedure with better surgical outcomes for patients with GC than GCO. However, high-quality randomized controlled trials are needed to confirm this benefit.

10.
Pharmacol Res ; 171: 105785, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311072

RESUMO

Gastric cancer (GC) development is a complex process displaying polytropic cell and molecular landscape within gastric tumor microenvironment (TME). Stromal cells in TME, including fibroblasts, endothelial cells, mesenchymal stem cells, and various immune cells, support tumor growth, metastasis, and recurrence, functioning as the soil for gastric tumorigenesis. Importantly, exosomes secreted by either stromal cells or tumor cells during tumor-stroma crosstalk perform as crucial transporter of agents including RNAs and proteins for cell-cell communication in GC pathogenesis. Therefore, given the distinct roles of exosomes secreted by various cell types in GC TME, increasing evidence has indicated that exosomes present as new biomarkers for GC diagnosis and prognosis and shed light on novel approaches for GC treatment.


Assuntos
Exossomos , Neoplasias Gástricas , Células Estromais , Microambiente Tumoral , Animais , Humanos
11.
Onco Targets Ther ; 14: 503-518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500626

RESUMO

PURPOSE: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review summarises the emerging role, potential targets or pathways and regulatory mechanisms of lncRNAs involved in chemoresistance and proposes a number of clinical implications of lncRNAs as novel therapeutic targets for GC. METHODS: Studies on lncRNAs involved in the chemoresistance of GC published until July 2020 in the PubMed and Web of Science databases were systematically reviewed and the expression form, role in chemoresistance, targets or pathways, corresponding drugs and potential mechanisms of relevant lncRNAs were summarised in detail. RESULTS: A total of 48 studies were included in this systematic review. Amongst these studies, 32 involved single drug resistance and 16 involved in multidrug resistance (MDR). The 48 studies collected described 38 lncRNAs in the drug-resistant cells of GC, including 33 upregulated and 5 downregulated lncRNAs. Cisplatin (DDP) was the most studied drug and lncRNA MALAT1 was the most studied lncRNA related to the chemoresistance of GC. The potential mechanisms of chemoresistance for lncRNAs in GC mainly included, amongst others, reduction of apoptosis, induction of autophagy, repair of DNA damage, promotion of epithelial-mesenchymal transition (EMT) and regulation of the related signalling pathways. CONCLUSION: LncRNAs play a vital role in the chemoresistance of GC and are novel therapeutic targets for the disease. Detailed chemoresistance mechanisms, translational studies and clinical trials on lncRNAs in GC are urgently needed.

13.
Am Surg ; 87(12): 1910-1919, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33377797

RESUMO

BACKGROUND: Indocyanine green (ICG) fluorescence angiography is a new technique that help surgeons to assess the blood perfusion of the anastomotic intestine. The aim of this study is to evaluate whether ICG fluorescence angiography can reduce the anastomotic leakage (AL) rate after colorectal anastomoses for rectal cancer (RC) patients. METHODS: Studies comparing AL rates between use and nonuse of ICG fluorescence angiography up to April 2020 were systematically searched from PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. A pooled analysis was performed for the available data regarding the baseline features, AL rate, and other surgical outcomes. ReMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted. RESULTS: Thirteen studies with a total of 2593 patients (1121 in the ICG group and 1472 in the control group) undergoing colorectal anastomoses after RC surgery were included. In the pooled analysis, the baseline data, operation time, and intraoperative blood loss in 2 groups were all comparable and without significant heterogeneity. However, the AL rate in the ICG group was significantly lower (OR .31; 95% CI .22-.44; P < .00001) than that in the control group. Additionally, ICG fluorescence angiography was associated with a decreased overall complication rate (OR .60; 95% CI .47-.76; P < .0001) in patients who undergo RC surgery. CONCLUSIONS: The present study revealed that ICG fluorescence angiography reduced AL rate after colorectal anastomoses for RC patients. However, more high-quality randomized controlled trials are needed to confirm this benefit.


Assuntos
Fístula Anastomótica/diagnóstico por imagem , Fístula Anastomótica/prevenção & controle , Colo/cirurgia , Corantes , Angiofluoresceinografia/métodos , Verde de Indocianina , Neoplasias Retais/cirurgia , Reto/cirurgia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Feminino , Humanos , Masculino
14.
J Zhejiang Univ Sci B ; 21(9): 749-751, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32893532

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was found initially in Wuhan, China in early December 2019. The pandemic has spread to 216 countries and regions, infecting more than 23310 000 people and causing over 800 000 deaths globally by Aug. 24, 2020, according to World Health Organization (https://www.who.int/emergencies/diseases/ novel-coronavirus-2019). Fever, cough, and dyspnea are the three common symptoms of the condition, whereas the conventional transmission route for SARS-CoV-2 is through droplets entering the respiratory tract. To date, infection control measures for COVID-19 have been focusing on the involvement of the respiratory system. However, ignoring potential faecal transmission and the gastrointestinal involvement of SARS-CoV-2 may result in mistakes in attempts to control the pandemic.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Fezes/virologia , Gastroenteropatias/virologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Betacoronavirus/genética , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Microbiologia Ambiental , Humanos , Modelos Biológicos , Pandemias , Pneumonia Viral/epidemiologia , RNA Viral/análise , RNA Viral/genética , SARS-CoV-2 , Eliminação de Partículas Virais
15.
Pharmacol Res ; 155: 104691, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32070721

RESUMO

Natural killer (NK) cells are immune cells which are able to kill tumor and virus-infected cells and play an important role in both innate immunity and acquired immunity. Tumor immunotherapy is an emerging model of tumor treatment in the clinic. It is a re-emerging type of anticancer immunotherapy with the purpose of killing tumor cells by modulating the body's immune function and enhancing the antitumor immunity in tumor microenvironment. At present, many immune cells including lymphokine-activated killer cells, NK cells, cytokine-induced killer cells, and dendritic cells are involved in tumor immunotherapy studies. NK cells, which lyse tumor cells without prior stimulation, has become a research hotspot in cancer immunotherapy for clinical application. In this article, we discussed the surface receptors of NK cells and the anticancer function of NK cells. We also reviewed the biological characteristics and the current research status of NK cells, their clinical application in cancer immunotherapy and its future perspectives.


Assuntos
Citocinas/uso terapêutico , Imunoterapia , Células Matadoras Naturais/imunologia , Neoplasias/terapia , Animais , Humanos , Neoplasias/imunologia , Receptores de Células Matadoras Naturais/imunologia
17.
J Mol Cell Cardiol ; 131: 20-28, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30998981

RESUMO

Angiotensin II (Ang II) modulates blood pressure via Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). The activation of AT2R relaxes vascular tone through opening large-conductance Ca2+-activated potassium (BKCa) channels in vascular smooth muscle cells (SMCs). In the present study, we studied the role of the AT2R-BKCa pathway in patients with hypertension. The mesenteric arterial SMCs (MSMCs) were obtained from normotensive patients (NP) and hypertensive patients (HP). BKCa currents were recorded with patch clamp and the expressions of mRNAs and proteins of AT1R/AT2R were analyzed by RT-PCR and Western blotting, respectively. Ang II significantly increased the macroscopic BKCa currents at the whole cell level, while increased the open probability and decreased the mean close time of BKCa channels at the single channel level with AT1R blockade by valsartan in NP. However, Ang II had no effect on the BKCa currents at the same condition in HP. Furthermore, the expressions of mRNA and protein of AT2R but not AT1R were markedly decreased in the MSMCs of HP compared to that of NP. The data suggest that AT2R is well functioned in the MSMCs in NP but not in HP and deficiency in the AT2R-BKCa pathway may contribute to the development of hypertension.


Assuntos
Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Artérias Mesentéricas/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Western Blotting , Células Cultivadas , Feminino , Humanos , Hipertensão/metabolismo , Técnicas In Vitro , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Masculino , Pessoa de Meia-Idade , Técnicas de Patch-Clamp , Receptor Tipo 2 de Angiotensina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Acta Pharm Sin B ; 9(2): 203-219, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30972274

RESUMO

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.

19.
J Cell Biochem ; 120(1): 56-70, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30246452

RESUMO

Endotoxin tolerance is defined as a reduced capacity of a cell to respond endotoxin (lipopolysaccharide, LPS) challenge after an initial encounter with endotoxin in advance. The body becomes tolerant to subsequent challenge with a lethal dose of endotoxin and cytokines release and cell/tissue damage induced by inflammatory reaction are significantly reduced in the state of endotoxin tolerance. The main characteristics of endotoxin tolerance are downregulation of inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and C-X-C motif chemokine 10 (CXCL10) and upregulation of anti-inflammatory cytokines such as IL-10 and transforming growth factor ß (TGF-ß). Therefore, endotoxin tolerance is often regarded as the regulatory mechanism of the host against excessive inflammation. Endotoxin tolerance is a complex pathophysiological process and involved in multiple cellular signal pathways, receptor alterations, and biological molecules. However, the exact mechanism remains elusive up to date. To better understand the underlying cellular and molecular mechanisms of endotoxin tolerance, it is crucial to investigate the comprehensive cellular signal pathways, signaling proteins, cell surface molecules, proinflammatory and anti-inflammatory cytokines, and other mediators. Endotoxin tolerance plays an important role in reducing the mortality of sepsis, endotoxin shock, and other endotoxin-related diseases. Recent reports indicated that endotoxin tolerance is also related to other diseases such as cystic fibrosis, acute coronary syndrome, liver ischemia-reperfusion injury, and cancer. The aim of this review is to discuss the recent advances in endotoxin tolerance mainly based on the cellular and molecular mechanisms by outline the current state of the knowledge of the involvement of the toll-like receptor 4 (TLR4) signaling pathways, negative regulate factor, microRNAs, apoptosis, chromatin modification, and gene reprogramming of immune cells in endotoxin tolerance. We hope to provide a new idea and scientific basis for the rational treatment of endotoxin-related diseases such as endotoxemia, sepsis, and endotoxin shock clinically.


Assuntos
Apoptose/imunologia , Lipopolissacarídeos , Choque Séptico , Transdução de Sinais , Animais , Humanos , Inflamação/imunologia , Inflamação/patologia , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/toxicidade , Choque Séptico/imunologia , Choque Séptico/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
20.
Front Pharmacol ; 9: 75, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29487524

RESUMO

Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1ß, TNF-α, and NO in the blood and TNF-α, IL-1ß, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while significantly increased the expression of SIgA in the intestinal tissues and/or MLN cells in SAP rats. Our results indicate that FTRAs could protect intestinal injury and improve intestinal mucosal barrier function through regulating immune function of SAP rats. Therefore, FTRAs may have the potential to be developed as the novel agent for the treatment of SAP clinically.

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