Burn ointment (BO) is a clinically useful medicine for the treatment of burns and scalds. However, there is no enough scientific evidence to report the effect of BO on wound healing and its analgesic ...and anti-inflammatory efficacy. The aim of this work was to evaluate the anti-inflammatory and analgesic efficacy of BO and to reveal the potential wound healing properties and related mechanisms of BO. In this work, the content of active ingredients of BO was determined by high-performance liquid chromatography (HPLC). Two animal models of inflammation were used to study its anti-inflammatory activity, and a hot plate method was used to evaluate its analgesic effect. In addition, mouse incision and rat burn models were used to investigate the effect of BO on the anti-inflammatory and wound healing mechanisms. The results showed that BO was safe for topical application, and BO could significantly inhibit auricular swelling in mice and paw swelling in rats and significantly prolong the latency period of paw licking in the hot plate experiment in mice. It can also accelerate wound healing and repair scars by promoting the formation of new epithelial tissues in rat burn models. In addition, BO significantly downregulated the serum level of TNF-α and significantly increased the serum levels of VEGF and TGF-β1. Also, BO promoted the expression of collagen I and increased the ratio in p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR pathways. Our results demonstrate the safety and efficacy of BO and suggest that activation of the PI3K/AKT/mTOR signaling pathway may play an important role in the promotion of wound healing by BO.
Triple positive breast cancer (TPBC) is one of the most aggressive breast cancer. Due to the unique cell phenotype, aggressiveness, metastatic potential and lack of receptors or targets, chemotherapy ...is the choice of treatment for TNBC. Doxorubicin (DOX), one of the representative agents of anthracycline chemotherapy, has better efficacy in patients with metastatic TNBC (mTNBC). DOX in anthracycline-based chemotherapy regimens have higher response rates. Nano-drug delivery systems possess unique targeting and ability of co-load, deliver and release chemotherapeutic drugs, active gene fragments and immune enhancing factors to effectively inhibit or kill tumor cells. Therefore, advances in nano-drug delivery systems for DOX therapy have attracted a considerable amount of attention from researchers. In this article, we have reviewed the progress of nano-drug delivery systems (e.g., Nanoparticles, Liposomes, Micelles, Nanogels, Dendrimers, Exosomes, etc.) applied to DOX in the treatment of TNBC. We also summarize the current progress of clinical trials of DOX combined with immune checkpoint inhibitors (ICIS) for the treatment of TNBC. The merits, demerits and future development of nanomedicine delivery systems in the treatment of TNBC are also envisioned, with the aim of providing a new class of safe and efficient thoughts for the treatment of TNBC.
α-Mangostin is a natural xanthone derivative isolated from Camellia atrophy (CA), commonly known as Lichuan black tea (LBT). The present study investigated the ameliorating effect and mechanism of ...α-mangostin on alcoholic gastric ulcers (GU) in rats. In vivo, α-mangostin relieved pathological symptoms. Moreover, α-mangostin regulated the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) and nuclear factor κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3)/caspase-1 pathways. Reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were significantly decreased and IL-10 were increased, the microtubule-associated protein light chain 3 (LC3)-II/LC3-I ratio was increased, p62 protein expression was decreased, and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression was down-regulated. The relevant mechanisms were validated using GSE-1 and RAW264.7 cells in an in vitro model. Furthermore, α-mangostin increased Ligilactobacillus and Muribaculum abundance as well as propionic acid and butyric acid contents. Therefore, α-mangostin possesses antioxidant and anti-inflammatory properties, and remodels intestinal flora dysbiosis through mechanisms that may involve regulation of the Nrf2/HO-1 pathway and NF-κB/NLRP3/caspase-1 pathway. It also increases propionic acid and butyric acid contents. This study provides novel evidence regarding the use of α-mangostin for treating GU.
Prunus mira Koehne (P. mira, Tibetan name: ཁམབུ།) is a kind of medicinal plant commonly used in Tibetan areas. The classic Tibetan medicine book Jingzhu Materia Medica records that “the nut oil from ...P. mira is used to cure loss of hair, eyebrows, beards, etc.” but the clinical experience has not been explored. Hair loss (alopecia) is a skin disease that becomes a common concern in Chinese society since it affects the appearance of a person. This paper studies the effectiveness of nut oil from P. mira in promoting hair growth and its working mechanism.
The content of different components in the nut oil from P. mira was determined by HPLC. Two hair removal methods (sodium sulfide and hair removal cream) were used to study the effect of different doses on hair growth in KM mice. Then select the effective group, and use C57BL/6 mice to determine the number of hair follicles, dermal thickness, β-catenin, GSK3β and Wnt10 b mRNA and protein expression.
The contents of α-tocopherol, β-sitosterol, Vitamin E, Oleic acid and linoleic acid in nut oil from P. mira growing in 12 different regions were determined by HPLC. The linearity reached 0.999. The RSD of precision, stability, repeatability, and sample recovery was less than 3%. The dose-effect relationship suggested that 30.13 and 14.07 mg medicinal material·(cm2·d)−1 oil promoted hair growth and the dose effect was positively correlated. 30.13 mg medicinal material·(cm2·d)−1 nut oil from P. mira can accelerate hair follicles into the anagen, increasing Wnt 10 b mRNA expression, β-catenin mRNA and protein expression, and GSK-3 β protein expression.
This study improved the quality control of nut oil from P. mira and found that it has the effect of promoting hair growth in mice. The working mechanism may be related to Wnt/β-catenin signaling pathway.
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5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical ...application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection.
5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy.
In this study, the WNT/β-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells.
These data underscored the activation of the WNT/β-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its ...expression pattern and function in tongue cancer is not clear.
The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model.
We found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients' lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo.
MMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background 5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its ...clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection. Methods 5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy. Results In this study, the WNT/beta-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells. Conclusions These data underscored the activation of the WNT/beta-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells. Keywords: WNT/beta-catenin pathway, Oral squamous cell carcinoma, 5-Fluorouracil, Chemoresistance, MSAB
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The structural design of vehicles plays an important role in improving vehicle safety and driving performance. In this study, the frame structure of a van-type electric truck was taken as a research ...object. Stress, strain, and modal analyses of this frame structure were performed using Abaqus, a finite element software, to verify the rationality and safety of the structural design. The frame structure was optimized by numerical analysis. The fourth beam was moved 524 mm forward between the installation points of the power battery pack and the rear lifting lug of the front leaf spring. Results showed that the optimized frame bending, the full-load braking condition, and the full-load torsional operating condition stresses decreased by 44.499%, 23.364%, and 31.303%, respectively. The bending stiffness of an optimized frame increased by 4.026%, whereas the front and rear torsional stiffnesses increased by 4.442% and 4.092%, respectively.
An efficient and facile synthesis for 2-aminobenzimidazoles and 2-aminobenzoxazoles has been reported. Thioureas prepared from the reaction of o-phenylenediamines or 2-aminophenols and isothiocyanate ...derivatives, underwent desulfurization reaction smoothly under mild conditions in the presence of Cu(OAc)
2
, and afforded a variety of N-heterocyclic compounds in moderate to good yields.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Matrix metalloproteinase-1 (MMP1) has an aberrant expression relevant to various behaviors of cancers. As dominant components of the tumor stroma, fibroblasts constitute an important source of Matrix ...metalloproteinase (MMPs) including mainly MMP1. The impacts of MMP1 derived from fibroblasts in tumor microenvironment, however, is not well defined. In this study, we demonstrated a part of crosstalk between fibroblasts and cancer cells that enhanced the invasiveness of cancer cells, IL8-induced activation of STAT3 signaling pathway as a key promoter to elevated MMP1 level in fibroblasts that supports the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells by extracellular matrix degradation. Importantly, once exposed to the inhibitor of STAT3 phosphorylation (TPCA-1), the enhanced induction of HNSCC cells invasion triggered by fibroblasts was significantly impaired.
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