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1.
Phytother Res ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837315

ABSTRACT

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

2.
Front Pharmacol ; 15: 1290888, 2024.
Article in English | MEDLINE | ID: mdl-38323080

ABSTRACT

Armeniacae semen amarum-seeds of Prunus armeniaca L. (Rosaceae) (ASA), also known as Kuxingren in Chinese, is a traditional Chinese herbal drug commonly used for lung disease and intestinal disorders. It has long been used to treat coughs and asthma, as well as to lubricate the colon and reduce constipation. ASA refers to the dried ripe seed of diverse species of Rosaceae and contains a variety of phytochemical components, including glycosides, organic acids, amino acids, flavonoids, terpenes, phytosterols, phenylpropanoids, and other components. Extensive data shows that ASA exhibits various pharmacological activities, such as anticancer activity, anti-oxidation, antimicrobial activity, anti-inflammation, protection of cardiovascular, neural, respiratory and digestive systems, antidiabetic effects, and protection of the liver and kidney, and other activities. In clinical practice, ASA can be used as a single drug or in combination with other traditional Chinese medicines, forming ASA-containing formulas, to treat various afflictions. However, it is important to consider the potential adverse reactions and pharmacokinetic properties of ASA during its clinical use. Overall, with various bioactive components, diversified pharmacological actions and potent efficacies, ASA is a promising drug that merits in-depth study on its functional mechanisms to facilitate its clinical application.

3.
Front Immunol ; 14: 1285550, 2023.
Article in English | MEDLINE | ID: mdl-37954597

ABSTRACT

Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.


Subject(s)
Acute Lung Injury , NF-kappa B , Mice , Rats , Humans , Animals , NF-kappa B/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Toll-Like Receptor 4/metabolism , Lipopolysaccharides/pharmacology , Pandemics , Mice, Inbred NOD , Signal Transduction , Acute Lung Injury/metabolism , Cytokines/metabolism
4.
Phytomedicine ; 114: 154792, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37028248

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a malignant affliction that burdens people globally. Overactivated Hedgehog signal is highly implicated in CRC pathogenesis. Phytochemical berberine exerts strong potency on CRC, with molecular mechanism elusive. PURPOSE: We sought to study berberine's anti-CRC action and explore its underlying mechanism based on Hedgehog signaling cascade. METHODS: In CRC HCT116 cells and SW480 cells treated with berberine, the proliferation, migration, invasion, clonogenesis, apoptosis and cell cycle were measured, with determination of Hedgehog signaling pathway activity. Following establishment of mouse model of HCT116 xenograft tumor, the efficacies of berberine on carcinogenesis, pathological manifestation and malignant phenotypes of CRC were examined, with analysis of Hedgehog signaling axis in HCT116 xenograft tumor tissues. Additionally, toxicological study of berberine was conducted on zebrafish. RESULTS: Berberine was discovered to suppress the proliferation, migration, invasion and clonogenesis of HCT116 cells and SW480 cells. Furthermore, berberine caused cell apoptosis and blockaded cell cycle at phase G0/G1 in CRC cells, with dampened Hedgehog signaling cascade. In HCT116 xenograft tumor of nude mice, berberine inhibited tumor growth, alleviated pathological score, and promoted apoptosis and cell cycle arrest in tumor tissues, through constraining Hedgehog signaling. The toxicological study of berberine on zebrafish indicated that berberine incurred damage to the liver and heart of zebrafish at high dosage and prolonged administration. CONCLUSIONS: Taken together, berberine may inhibit the malignant phenotypes of CRC through diminishing Hedgehog signaling cascade. However, the potential adverse reactions should be taken into account upon abuse of berberine.


Subject(s)
Berberine , Colorectal Neoplasms , Mice , Animals , Humans , Hedgehog Proteins , Berberine/pharmacology , Zebrafish , Mice, Nude , Colorectal Neoplasms/drug therapy , Cell Proliferation , HCT116 Cells , Cell Movement , Cell Line, Tumor , Apoptosis
5.
J Agric Food Chem ; 71(9): 3981-3993, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36826439

ABSTRACT

Overwhelming evidence points to an abnormally active Wnt/ß-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/ß-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/ß-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/ß-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/ß-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.


Subject(s)
Colorectal Neoplasms , Wnt Signaling Pathway , Humans , Mice , Animals , Down-Regulation , beta Catenin/genetics , beta Catenin/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Ursolic Acid
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1015605

ABSTRACT

Interleukin-6 (IL-6) is a spreading pleiotropic cytokine, with both anti-inflammatory and proinflammatory effects. It not only participates in the body immune responses but also is involved in the biological regulative processes among different organs, tissues, and cells. IL-6 has both anti-inflammatory and pro-inflammatory effects. In the early stage of pathogen infection, IL-6 plays an anti-inflammatory role in the body, and its level is moderately increased in the body to resist inflammation and maintain internal homeostasis. However, a large amount of IL-6 release can cause excessive inflammation and trigger other pathological changes in the body. Il-6 also has the dual effect of stimulating the synthesis and degradation of skeletal muscle protein in regulating skeletal muscle mass. As an important locomotive organ, skeletal muscle is also one of the key targets of IL-6. IL-6 takes part in the biological control of skeletal muscle hypertrophy through regulating muscle satellite cell proliferation and differentiation under specific stresses. In addition IL-6 is also associated with skeletal muscle atrophy induced by aging and other pathological stresses. In addition, during exercise stress, skeletal muscle can also serve as an endocrine organ to secrete and release IL-6 that facilitates the "crosstalk" between skeletal muscle and other organs or tissues. As IL-6 plays as a versatile role in our body, this paper reviews the research progress of the mechanism of IL-6 in the regulation of skeletal muscle mass, which may provide theoretical support for revealing the molecular mechanism of skeletal muscle stresses and adaptations.

7.
Biomed Pharmacother ; 156: 113956, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36411666

ABSTRACT

Nowadays, one of the leading causes of death in humans is cancer, which is still on the rise globally and is in great need of intense study on the pathogenic mechanism and effective therapy. Epigenetics is a discipline that studies heritable changes in gene expression without alteration of DNA sequence. Epigenetic changes mainly involve DNA methylation, histone modifications and non-coding RNA (ncRNA) expression, which are interconnected to play a crucial role in the initiation and progression of various malignancies. Curcumin is a type of plant-derived polyphenolic compound with strong bioactivity against various disorders, particularly cancer. Retrieving commonly used databases such as PubMed, Google Scholar and CNKI, we summarized recent advances in the efficacy of curcumin on cancer and its epigenetic regulation in terms of DNA methylation, histone modifications and ncRNA expression. Furthermore, we also focused on improving the bioavailability of curcumin by development of novel curcumin analogs with high bioavailability, nanoparticles-loaded drug delivery system for curcumin, and combination therapy of curcumin with other agents. This review provides comprehensive insights into the molecular mechanisms, on the basis of epigenetic regulation, underlying the clinical application of curcumin in cancer.


Subject(s)
Curcumin , Neoplasms , Humans , Epigenesis, Genetic , Curcumin/pharmacology , Curcumin/therapeutic use , Neoplasms/drug therapy , Neoplasms/genetics , DNA Methylation/genetics , Protein Processing, Post-Translational
8.
Biomed Pharmacother ; 154: 113559, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35994817

ABSTRACT

Mentha (also known as peppermint), a genus of plants in the taxonomic family Lamiaceae (mint family), is widely distributed throughout temperate regions of the world. Mentha contains various constituents that are classified as peppermint essential oil (PEO) and non-essential components. PEO, consisting mainly of menthol, menthone, neomenthol and iso-menthone, is a mixture of volatile metabolites with anti-inflammatory, antibacterial, antiviral, scolicidal, immunomodulatory, antitumor, neuroprotective, antifatigue and antioxidant activities. Mounting evidence indicates that PEO may pharmacologically protect gastrointestinal, liver, kidney, skin, respiratory, brain and nervous systems, and exert hypoglycemic and hypolipidemic effects. Clinically, PEO is used for gastrointestinal and dermatological diseases, postoperative adjuvant therapy and other fields. This review aims to address the advances in the extraction and isolation of PEO, its biological activities, pharmacological effects, toxicity and applications, with an emphasis on the efficacy of PEO on burn wounds and psoriasis, providing a comprehensive foundation for research, development and application of PEO in future.


Subject(s)
Lamiaceae , Oils, Volatile , Mentha piperita/metabolism , Menthol , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use
9.
Mol Cancer ; 21(1): 144, 2022 07 14.
Article in English | MEDLINE | ID: mdl-35836256

ABSTRACT

BACKGROUND: The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/ß-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of ß-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). OBJECTIVE: Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. METHODS: Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. RESULTS: Wnt signaling pathways include: Wnt/ß-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. CONCLUSION: The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Epithelial-Mesenchymal Transition , Humans , Tumor Microenvironment , Wnt Signaling Pathway , beta Catenin/metabolism
10.
Phytomedicine ; 103: 154227, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35679795

ABSTRACT

BACKGROUND: A growing body of evidence reveals that dysregulation of Hedgehog signaling pathway and dysbiosis of gut microbiota are associated with the pathogenesis of colorectal cancer (CRC). Berberine, a botanical benzylisoquinoline alkaloid, possesses powerful activities against various malignancies including CRC, with the underlying mechanisms to be illuminated. PURPOSE: The present study investigated the potencies of berberine on CRC and deciphered the action mechanisms in the context of Hedgehog signaling cascade and gut microbiota. METHODS: The effects of berberine on the malignant phenotype, apoptosis, cell cycle and Hedgehog signaling of CRC cells were examined in vitro. In azoxymethane/dextran sulfate sodium-caused mouse CRC, the efficacies of berberine on the carcinogenesis, pathological profile, apoptosis, cell cycle and Hedgehog signaling were determined in vivo. Also, the influences of berberine on gut microbiota in CRC mice were assessed by high-throughput DNA sequencing analysis of 16S ribosomal RNA of fecal microbiome in CRC mice. RESULTS: In the present study, berberine was found to dampen the proliferation, migration, invasion and colony formation of CRC cells, without toxicity to normal colonic cells. Additionally, berberine induced apoptosis and arrested cell cycle at G0/G1 phase in CRC cells, accompanied by reduced Hedgehog signaling pathway activity in vitro. In mouse CRC, berberine suppressed tumor growth, ameliorated pathological manifestations, and potentially induced the apoptosis and cell cycle arrest of CRC, with lowered Hedgehog signaling cascade in vivo. Additionally, berberine decreased ß-diversity of gut microbiota in CRC mice, without influence on α-diversity. Berberine also enriched probiotic microbes and depleted pathogenic microbes, and modulated the functionality of gut microbiota in CRC mice. CONCLUSIONS: Overall, berberine may suppress colorectal cancer, orchestrated by down-regulation of Hedgehog signaling pathway activity and modulation of gut microbiota.


Subject(s)
Berberine , Colorectal Neoplasms , Gastrointestinal Microbiome , Animals , Azoxymethane , Berberine/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/microbiology , Gastrointestinal Microbiome/drug effects , Hedgehog Proteins/metabolism , Mice , Signal Transduction/drug effects
11.
Phytother Res ; 36(9): 3555-3570, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35708264

ABSTRACT

It is being brought to light that smoothened (SMO)-independent non-canonical Hedgehog signaling is associated with the pathogenesis of various cancers. Ursolic acid (UA), a pentacyclic triterpenoid present in many medicinal herbs, manifests potent effectiveness against multiple malignancies including colorectal cancer (CRC). In our previous study, UA was found to protect against CRC in vitro by suppression of canonical Hedgehog signaling cascade. Here, the influence of UA on SMO-independent non-canonical Hedgehog signaling in CRC was investigated in the present study, which demonstrated that UA hampered the proliferation and migration, induced the apoptosis of HCT-116hSMO- cells with SMO gene knockdown, accompanied by the augmented expression of the suppressor of fused (SUFU), and lessened levels of MYC (c-Myc), glioma-associated oncogene (GLI1) and Sonic Hedgehog (SHH), and lowered phosphorylation of protein kinase B (PKB, AKT), suggesting that UA diminished non-canonical Hedgehog signal transduction in CRC. In HCT-116hSMO- xenograft tumor, UA ameliorated the symptoms, impeded the growth and caused the apoptosis of CRC, with heightened SUFU expression, and abated levels of MYC, GLI1, and SHH, and mitigated phosphorylation of AKT, indicating that UA down-regulated non-canonical Hedgehog signaling cascade in CRC. Taken together, UA may alleviate CRC by suppressing AKT signaling-dependent activation of SMO-independent non-canonical Hedgehog pathway.


Subject(s)
Colorectal Neoplasms , Triterpenes , Animals , Cell Proliferation , Colorectal Neoplasms/drug therapy , Hedgehog Proteins/metabolism , Humans , Oleanolic Acid/analogs & derivatives , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Triterpenes/pharmacology , Zinc Finger Protein GLI1/genetics , Ursolic Acid
12.
Phytomedicine ; 98: 153972, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35151214

ABSTRACT

BACKGROUND: Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) and mainly develops from long-term intestinal inflammation. Mounting evidence reveals that activated Hedgehog signaling pathway plays a vital role in the pathogenesis of CRC. Scutellarin is a type of phytochemical flavonoid with a powerful efficacy on various malignancies, including CRC. AIM: Here, we studied the therapeutic effect of scutellarin on CRC and its direct regulating targets. METHODS: The CAC model in mice was established by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by detection of the efficacies of scutellarin on the carcinogenesis, apoptosis, inflammation, Hedgehog signaling cascade and complicated inflammatory networks in CAC tissues of mice. In CRC SW480 cells, the effects of scutellarin on malignant phenotype, apoptosis and Hedgehog signaling were examined. In TNF-α-stimulated IEC-6 intestinal epithelial cells, the actions of scutellarin on inflammatory response and Hedgehog signals were assessed as well. RESULTS: Scutellarin significantly ameliorated AOM/DSS-caused CAC in mice and induced apoptosis in CAC tissues of mice, by inhibiting NF-κB (nuclear factor kappa B) -mediated inflammation and Hedgehog signaling axis. RNA-seq and transcriptome analysis indicated that scutellarin regulated complicated inflammatory networks in mouse CAC. Also, scutellarin suppressed the proliferation, migration, colony formation, and induced apoptosis of SW480 cells by down-regulation of Hedgehog signaling pathway activity. Additionally, scutellarin lessened NF-κB-mediated inflammatory response in TNF-α-stimulated IEC-6 cells, by attenuating Hedgehog signaling cascade. CONCLUSION: Scutellarin potently ameliorates CAC by suppressing Hedgehog signaling pathway activity, underpinning the promising application of scutellarin to CRC in clinical settings.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-957853

ABSTRACT

Objective:To summarize the institutional experiences of treating vascular complications caused by donor-derived infection(DDI)after kidney transplantation(KT).Methods:From January 1, 2015 to December 31, 2020, clinical data were retrospectively reviewed for 6 cases of vascular complications caused by DDI.Age, gender, surgical approaches, immunity induction therapy, immune suppression therapy, infection prevention, onset time of complication, type of complications, infection pathogens, therapeutic protocols and prognoses were summarized.Results:Six patients developed vascular complications caused by DDI in 997 KT recipients with an overall morbidity rate of 0.6%.In 3 cases, carbapenem resistant Klebsiella pneumoniae were positive in culture of secretion and blood samples.And Candida albicans was detected by blood cultures and pathological examinations.One case of antibiotic resistant Staphylococcus aureus was detected by blood culture.Among 3 cases of transplant kidney artery pseudoaneurysm on interventional therapy, there were curing(1 case)and immediate recurrent infection(2 cases). The latter two eventually died by cardiac complications.In 2 cases of arterial hemorrhage, graft nephrectomy was followed by hemodialysis.One case of transplanted renal artery stenosis was successfully cured by artery stenting and survived with normal graft function so far.Conclusions:Interventional endovascular therapy and open surgery are indicated for vascular complications caused by DDI post-KT.Interventional therapy may boost the odds of rescuing transplant kidney.However, clinicians should watch out for the risk of recurrent infection.Open surgery is an effective tool of eliminating infected focus.Preserving transplant kidney or nephrectomy may be adopted on the basis of specific conditions.

14.
Front Immunol ; 11: 506275, 2020.
Article in English | MEDLINE | ID: mdl-33133065

ABSTRACT

Ubiquitin-specific peptidase 10 (USP10) protein is a deubiquitination enzyme involved in many important biological processes. However, the function of USP10 in hepatic ischaemic/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP10 in hepatic I/R injury. USP10 Heterozygote mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP10 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP10 was significantly downregulated in the livers of mice after hepatic I/R injury and in hepatocytes subjected to hypoxia/reoxygenation stimulation. USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-κB signalling pathway and increased hepatocyte apoptosis. Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury in vitro and in vivo. Mechanistically, our study demonstrated that USP10 knockdown exerted its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor ß-activated kinase 1 (TAK1)-JNK/p38 signalling pathways. TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function in vitro. In conclusion, our study demonstrated that USP10 plays a protective role in hepatic I/R injury by inhibiting the activation of the TAK1-JNK/p38 signalling pathways. Modulation of USP10/TAK1 might be a promising strategy to prevent this pathological process.


Subject(s)
Liver Diseases/immunology , Liver/immunology , MAP Kinase Kinase Kinases/immunology , MAP Kinase Signaling System/immunology , Reperfusion Injury/immunology , Ubiquitin Thiolesterase/immunology , Animals , Liver/pathology , Liver Diseases/genetics , Liver Diseases/pathology , Liver Diseases/prevention & control , MAP Kinase Kinase Kinases/genetics , MAP Kinase Signaling System/genetics , Male , Mice , Reperfusion Injury/genetics , Reperfusion Injury/pathology , Reperfusion Injury/prevention & control , Ubiquitin Thiolesterase/genetics
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-870568

ABSTRACT

Objective:To summarize the clinical experiences of managing patients with novel coronavirus(2019-nCoV) infection after kidney transplantation.Methods:Clinical data were retrospectively analyzed for two patients with 2019-nCoV infection after renal transplantation in January 2020. Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months post-transplantation. CT imaging showed multiple patchy ground-glass opacities of both lungs. Case 2 was a 59-year-old male who screened positive for 2019-nCoV nucleic acid due to fever at 9 days post-transplantation and he showed no clinical manifestations of pneumonia. After a definite diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium plus linezolid for anti-infection, gamma globulin for enhancing immunity, methylprednisolone for controlling inflammatory responses and antiviral regimens of arbidol tablets plus lopina-velitonavir tablets. Case 2 was isolated in a single room. The treatment plan included cefoperazone sulbactam sodium for anti-infection, gamma globulin for enhancing immunity, arbidol for antiviral therapy and other symptomatic measures.Results:During a follow-up period of 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test of nasopharyngeal swab turned negative and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms and nucleic acid test of nasopharyngeal swab turned negative thrice.Conclusions:Renal transplant recipients should take precautions to avoid exposure to high-risk environments. A definite diagnosis should be made on the basis of clinical manifestations and results of nucleic acid test and pulmonary imaging. Currently there is no effective antiviral agent and symptomatic treatment is a major option.

16.
Chinese Medical Journal ; (24): 2653-2659, 2020.
Article in English | WPRIM (Western Pacific) | ID: wpr-877873

ABSTRACT

BACKGROUND@#Liver fibrosis (LF) continues to develop and eventually progresses to cirrhosis. However, LF and early-stage cirrhosis (ESC) can be reversed in some cases, while advanced cirrhosis is almost impossible to cure. Advances in quantitative imaging techniques have made it possible to replace the gold standard biopsy method with non-invasive imaging, such as radiomics. Therefore, the purpose of this study is to develop a radiomics model to identify LF and ESC.@*METHODS@#Patients with LF (n = 108) and ESC (n = 116) were enrolled in this study. As a control, patients with healthy livers were involved in the study (n = 145). Diffusion-weighted imaging (DWI) data sets with three b-values (0, 400, and 800 s/mm) of enrolled cases were collected in this study. Then, radiomics features were extracted from manually delineated volumes of interest. Two modeling strategies were performed after univariate analysis and feature selection. Finally, an optimal model was determined by the receiver operating characteristic area under the curve (AUC).@*RESULTS@#The optimal models were built in plan 1. For model 1 in plan 1, the AUCs of the training and validation cohorts were 0.973 (95% confidence interval [CI] 0.946-1.000) and 0.948 (95% CI 0.903-0.993), respectively. For model 2 in plan 1, the AUCs of the training and validation cohorts were 0.944, 95% CI 0.905 to 0.983, and 0.968, 95% CI 0.940 to 0.996, respectively.@*CONCLUSIONS@#Radiomics analysis of DWI images allows for accurate identification of LF and ESC, and the non-invasive biomarkers extracted from the functional DWI images can serve as a better alternative to biopsy.


Subject(s)
Humans , Diffusion Magnetic Resonance Imaging , Liver Cirrhosis/diagnostic imaging , Machine Learning , ROC Curve , Retrospective Studies
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008555

ABSTRACT

Indigenous knowledge and traditional culture for sustainable use of native plants in Juenang cultural region of Rangtang county, Aba Zang and Qiang Prefecture of Sichuan province, have been characterized in this paper followed the principles and methods of ethnobotany. The results indicate that 38 species from 27 families(including 6 species of fungi) are ethnobotanically used commonly in this area. Of 38 species of the native plants, 13 species from 12 families are collected for eatables and vegetables, 12 families and 16 species of indigenous plants for medicinal and edible use, 4 species from 4 families for decoration, 4 species from 4 families used for building materials or firewood, and 1 species from 1 families used for religious folklore. Under the influence of Juenang culture and Tibetan culture, indigenous knowledge such as instinctive reverence and gratitude for nature, protection ecological environment and habitats, and moderate use of natural resources(especially wild bioresource), have been gotten passed on from generation to generation in Juenang culture region of Rangtang county, which is of great significance to the protection of local bioresources and environment, including ethnic medicinal plants, and also to provide practical guidance for biodiversity conservation and ecological restoration in those alpine ecological vulnerable areas.


Subject(s)
Humans , Biodiversity , China , Conservation of Natural Resources , Ethnobotany , Fungi/classification , Knowledge , Phytotherapy , Plants, Medicinal/classification
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008498

ABSTRACT

Study the growth and development process of rhizomes(bamboo-like part) of Notopterygium incisum and the changes of carbohydrate, endogenous hormones and secondary metabolites, and provide theoretical guidance for the formation of high-quality N. incisum medicinal commodities under artificial cultivation. The One-year-old seedlings were transplanted to the original habitat,and the growth and physiological characteristics of N. incisum were dynamically monitored. The results showed that: ① Seedlings transplanted to the original habitat in spring could form rhizomes(bamboo-like part) in the same year. ② After 60 days of transplantation, the root length and root diameter of underground part of N. incisum had increased rapidly, and carbohydrate content in roots and rhizomes had accumulated rapidly. After 120 days of transplantation, the roots and rhizomes of underground part had grown slowly, and starch content in roots and rhizomes increased continuously, while sucrose and total soluble sugar content decreased gradually. ③ The content of abscisic acid(ABA) in rhizomes decreased firstly and then increased, while the indole acetic acid(IAA) content stabilized firstly and then increased rapidly, and the contents of gibberellin(GA_3) and zeatin riboside(ZR) continued to increase. ④ The content of notopterol in rhizomes was higher than that in roots, while the content of isoimperatorin was lower than that in roots, but the total content of the both in rhizomes was higher than that in roots. Therefore, N. incisum can form rhizomes with high content of secondary metabolites under wild tending, and the growth and development of rhizomes are closely related to changes in carbohydrates and are regulated by related endogenous hormones.


Subject(s)
Apiaceae/growth & development , Ecosystem , Phytochemicals/analysis , Plant Roots/growth & development , Plants, Medicinal/growth & development , Rhizome/growth & development , Secondary Metabolism , Seedlings/growth & development
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-811566

ABSTRACT

Objective@#To investigate the clinical experience of patients with novel coronavirus (2019-ncov) infection after kidney transplantation.@*Method@#Clinical data of two patients with 2019-nCoV infection after renal transplantationin Jan 2020 Renmin Hospital of Wuhan Universiyt were retrospectively analyzed.Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months after transplantation. CT imaging showed multiple patchy ground-glass images of both lungs. Case 2 was a 59-year-old male, who was screened positive for 2019-nCoV nucleic acid due to fever at 9 days after renal transplantation and showed no clinical manifestations of pneumonia. After diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium + linezolid to resist infection, gamma globulin to enhance immunity function, methylprednisolone to control inflammatory response, antiviral regimens including arbidol tablets + lopina-velitonavir tablets. Case 2 was treated with isolated treatment in a single room. The treatment plan included anti-infection (cefoperazone sulbactam sodium), enhancing immunity function (gamma globulin), antivirus therapy with arbidol and other symptomatic treatment.@*Result@#Follow up with 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test with nasopharyngeal swabs turned negative, and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms, and the nucleic acid test of nasopharyngeal swabs turned negative for 3 times.@*Conclusion@#Renal transplant recipients should receive fine protection to avoid exposure to high-risk environments. Diagnosis should be defined with combination of clinical manifestations, nucleic acid test and pulmonary imaging. At present, there are no antiviral drugs and symptomatic treatment is the main choice.

20.
Organ Transplantation ; (6): 185-2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-817592

ABSTRACT

In December 2019, a number of cases of pneumonia with unknown causes were successively reported in multiple hospitals in Wuhan City, Hubei Province, China. The pathogen is a novel coronavirus, which can lead to novel coronavirus pneumonia (COVID-19) and even threaten the patients' lives. In the following, the COVID-19 epidemic is spreading rapidly in many provinces and cities. It is particularly important to summarize and analyze the clinical characteristics of COVID-19 in solid organ transplantation (SOT) recipients and to optimize the prevention, early diagnosis and treatment strategies. Therefore, we organized Chinese experts in the field of organ transplantation to draft this article according to the characteristics of lung infection of SOT recipients and the characteristics of current COVID-19 by referring to relevant guidelines and specifications at home and abroad, aiming to provide reference for transplant physicians in China. This management strategy will be revised at any time with the deepening understanding of the COVID-19 infection.

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