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2.
Molecules ; 29(2)2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38257324

ABSTRACT

Despite advancements in analytical technologies, the complex nature of cosmetic matrices, coupled with the presence of diverse and trace unauthorized additives, hinders the application of these technologies in cosmetics analysis. This not only impedes effective regulation of cosmetics but also leads to the continual infiltration of illegal products into the market, posing serious health risks to consumers. The establishment of cosmetic regulations is often based on extensive scientific experiments, resulting in a certain degree of latency. Therefore, timely advancement in laboratory research is crucial to ensure the timely update and adaptability of regulations. A comprehensive understanding of the composition of cosmetic matrices and their pretreatment technologies is vital for enhancing the efficiency and accuracy of cosmetic detection. Drawing upon the China National Medical Products Administration's 2021 Cosmetic Classification Rules and Classification Catalogue, we streamline the wide array of cosmetics into four principal categories based on the following compositions: emulsified, liquid, powdered, and wax-based cosmetics. In this review, the characteristics, compositional elements, and physicochemical properties inherent to each category, as well as an extensive overview of the evolution of pretreatment methods for different categories, will be explored. Our objective is to provide a clear and comprehensive guide, equipping researchers with profound insights into the core compositions and pretreatment methods of cosmetics, which will in turn advance cosmetic analysis and improve detection and regulatory approaches in the industry.


Subject(s)
Cosmetics , China , Industry , Powders , Technology
3.
Anal Chim Acta ; 1274: 341568, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37455080

ABSTRACT

Sesquiterpene pyridine alkaloids (SPAs) are bioactive analogues derived from the genus Tripterygium and have anti-inflammatory and anti-rheumatic properties. Attributed to the similar sesquiterpene structures, the total SPAs showed severe peak overlap in 1D NMR and HPLC, leading to difficulties in identification and quantification. Interestingly, the application of band-selective HSQC NMR that specifically excited the region corresponding to the H-3 of SPAs prompted a signal separation of the total SPAs. Based on the high resolution, 23 SPAs were identified from the band-selective HSQC spectrum. The coupling constants (JCH, JHH) and relaxation times (T1, T2) of SPAs were measured, and it was found that they caused less than 1% attenuation of the HSQC signals, so the HSQC signals of SPAs had almost uniform responses. The concentrations of 23 SPAs were determined by standard curve method, using wilforgine as the calibration. In addition, we extended the pulse length-based concentration determination (PULCON) as a more efficient external standard method to the band-selective HSQC spectrum, and the results showed that the concentrations of alkaloids determined by PULCON were consistent with those measured by standard curve method. The developed quantification approach was validated according to the <761> of United States Pharmacopoeia (USP), demonstrating that the established band-selective HSQC approach is reliable for the rapid quantification of analogues in botanical extracts.


Subject(s)
Alkaloids , Sesquiterpenes , Tripterygium/chemistry , Alkaloids/chemistry , Magnetic Resonance Spectroscopy , Sesquiterpenes/chemistry , Pyridines/chemistry
4.
Anesth Analg ; 137(2): 399-408, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37267129

ABSTRACT

BACKGROUND: The effectiveness and safety of opioid-free anesthesia (OFA) regimens in distinct types of surgeries remain controversial. In this study, we investigated whether OFA could reduce the occurrence of chronic postoperative pain in patients receiving video-assisted thoracoscopic surgery (VATS). METHODS: We conducted a 2-center, randomized, controlled trial from September 2021 to January 2022. A total of 162 lung tumor patients scheduled to undergo VATS were randomly divided into an opioid-based anesthesia (OA) group and an OFA group. The OA group received general anesthesia combined with thoracic epidural block using morphine, while the OFA group received general anesthesia combined with thoracic epidural block using esketamine. Patient-controlled epidural analgesia (PCEA) was used after surgery (ropivacaine and morphine for the OA group versus ropivacaine and esketamine for the OFA group). The primary end point was chronic pain rates at 3 months after VATS, which were analyzed using a logistic regression model. The secondary end points were chronic pain rates at 6 months, acute pain rates at 24 hours and 48 hours postoperatively, postoperative side effects, and perioperative variables. RESULTS: The final analysis included 159 patients. Acute postoperative pain at 24 hours occurred in 0 of the 79 (0%) patients in the OA group and 10 of the 80 (17.5%) patients in the OFA group (odds ratio, 52.14; 95% confidence interval [CI], 6.47-420.10; P < .001). Acute postoperative pain at 48 hours occurred in 3 of the 79 (3.8%) patients in the OA group and 2 of the 80 (2.5%) patients in the OFA group (odds ratio, 2.07; 95% CI, 0.99-4.32; P = .053). In this study, none of the patients had moderate or severe pain in either group at 3 and 6 months postsurgically. Mild chronic postoperative pain at 3 months occurred in 27 of the 79 (34.2%) patients in the OA group and 14 of the 80 (17.5%) patients in the OFA group (odds ratio, 3.52; 95% CI, 1.49-8.31; P = .004). At 6 months, mild chronic pain still occurred in 23 of the 79 (29.1%) patients in the OA group and 9 of the 80 (11.3%) patients in the OFA group (odds ratio, 5.55; 95% CI, 2.01-15.33; P = .001). In addition, the OFA group included fewer patients with side effects, including nausea, vomiting, and pruritus, within 48 hours after surgery. CONCLUSIONS: Replacement of opioids by esketamine, intraoperatively as intravenous injection and epidural infusion and postoperatively as epidural infusion, reduces the incidence of mild chronic postoperative pain and side effects in patients after VATS.


Subject(s)
Analgesia, Epidural , Anesthesia, Epidural , Chronic Pain , Humans , Analgesics, Opioid/adverse effects , Ropivacaine/therapeutic use , Anesthetics, Local/adverse effects , Chronic Pain/drug therapy , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Morphine/adverse effects , Anesthesia, Epidural/adverse effects , Analgesia, Epidural/adverse effects , Thoracic Surgery, Video-Assisted/adverse effects
5.
Surg Endosc ; 36(12): 9113-9122, 2022 12.
Article in English | MEDLINE | ID: mdl-35773604

ABSTRACT

BACKGROUND: The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes for three-stage minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were consecutively enrolled, and were randomly divided into 2 groups: ERAS+group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of stay (LOS) and time to ambulation after the surgery. The perioperative results including the Surgical Apgar Score (SAS) and Visualized Analgesia Score (VAS) were also collected and compared. RESULTS: A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Postoperatively, lower morbidity and pulmonary complication rate were recorded in the ERAS+ group (33.3% vs. 51.7%; p = 0.04, 16.7% vs. 32.8%; p = 0.04), while the incidence of anastomotic leakage remained comparable (11.7% vs. 15.5%; p = 0.54). There was an earlier ambulation (3 [2-3] days vs. 3 [3-4] days, p = 0.001), but comparable LOS (10 [9-11.25] days vs. 10 [9-13] days; p = 0.165) recorded in ERAS+ group. The ERAS protocol led to close scores in both SAS (7.80 ± 1.03 vs. 8.07 ± 0.89, p = 0.21) and VAS (1.74 ± 0.85 vs. 1.78 ± 1.06, p = 0.84). CONCLUSIONS: Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower pulmonary complications, without a change in anastomotic leakage or length of hospital stay. Further studies on minimizing leakage should be addressed in ERAS for MIE.


Subject(s)
Esophageal Neoplasms , Esophagectomy , Humans , Esophagectomy/methods , Anastomotic Leak/surgery , Treatment Outcome , Esophageal Neoplasms/surgery , Esophageal Neoplasms/complications , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Minimally Invasive Surgical Procedures/methods
6.
Front Pharmacol ; 13: 849101, 2022.
Article in English | MEDLINE | ID: mdl-35712709

ABSTRACT

Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by synovial inflammation in multiple joints. Triptolide (TP) is a disease-modifying anti-rheumatic drug (DMARD) highly effective in patients with RA and has anti-inflammatory properties. However, its clinical application has been limited owing to practical disadvantages. In the present study, hyaluronic acid (HA) hydrogel-loaded RGD-attached gold nanoparticles (AuNPs) containing TP were synthesized to alleviate the toxicity and increase therapeutic specificity. The hydrogels can be applied for targeted photothermal-chemo treatment and in vivo imaging of RA. Hydrogel systems with tyramine-modified HA (TA-HA) conjugates have been applied to artificial tissue models as surrogates of cartilage to investigate drug transport and release properties. After degradation of HA chains, heat was locally generated at the inflammation region site due to near-infrared resonance (NIR) irradiation of AuNPs, and TP was released from nanoparticles, delivering heat and drug to the inflamed joints simultaneously. RA can be penetrated with NIR light. Intraarticular administration of the hydrogels containing low dosage of TP with NIR irradiation improved the inflamed conditions in mice with collagen-induced arthritis (CIA). Additionally, in vitro experiments were applied to deeply verify the antirheumatic mechanisms of TP-PLGA-Au@RGD/HA hydrogels. TP-PLGA-Au@RGD/HA hydrogel treatment significantly reduced the migratory and invasive capacities of RA fibroblast-like synoviocytes (RA-FLS) in vitro, through the decrease of phosphorylation of mTOR and its substrates, p70S6K1, thus inhibiting the mTOR pathway.

7.
Cell Biol Toxicol ; 38(6): 945-961, 2022 12.
Article in English | MEDLINE | ID: mdl-35040016

ABSTRACT

Covalent binding of reactive metabolites formed by drug metabolic activation with biological macromolecules is considered to be an important mechanism of drug metabolic toxicity. Recent studies indicate that the endoplasmic reticulum (ER) could play an important role in drug toxicity by participating in the metabolic activation of drugs and could be a primarily attacked target by reactive metabolites. In this article, we summarize the generation and mechanism of reactive metabolites in ER stress and their associated cell death and inflammatory cascade, as well as the systematic modulation of unfolded protein response (UPR)-mediated adaptive pathways.


Subject(s)
Apoptosis , Drug-Related Side Effects and Adverse Reactions , Humans , Unfolded Protein Response , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Stress , Drug-Related Side Effects and Adverse Reactions/metabolism
8.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3165-3170, 2021 Jun.
Article in Chinese | MEDLINE | ID: mdl-34467709

ABSTRACT

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.


Subject(s)
Aptamers, Nucleotide , Nucleic Acids , Drug Delivery Systems , Medicine, Chinese Traditional , RNA, Small Interfering
9.
Am J Cancer Res ; 11(7): 3445-3460, 2021.
Article in English | MEDLINE | ID: mdl-34354854

ABSTRACT

Paclitaxel is a widely used anti-tumor chemotherapeutic drug. Solvent-based paclitaxel causes bone marrow suppression, allergic reactions, neurotoxicity and systemic toxicity, which are associated with non-specific cytotoxicity and side effects of fat-soluble solvents. Studies have explored various new nano-drug strategies of paclitaxel, including nanoparticle albumin-bound paclitaxel (nab-paclitaxel) to improve the water solubility and safety of paclitaxel. Nab-paclitaxel is a targeted solvent-free formulation that inhibits microtubule depolymerization to anticancer. It is easily taken up by tumor and immune cells owing to the nano-scaled size and superior biocompatibility. The internalized nab-paclitaxel exhibits significant immunostimulatory activities to promote cancer-immunity cycle. The aim of this study was to explore the synergistic effect of nab-paclitaxel in tumor antigen presentation, T cell activation, reversing the immunosuppressive pattern of tumor microenvironment (TME), and the synergistic effect with cytotoxic lymphocytes (CTLs) in clearance of tumor cells. The effects of nab-paclitaxel on modulation of cancer-immunity cycle, provides potential avenues for combined therapeutic rationale to improve efficacy of immunotherapy.

10.
Eur J Med Chem ; 221: 113519, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-33984805

ABSTRACT

Arsenic (As), as well as its various compounds have been widely used for nearly 4000 years either as drugs or poisons. These compounds are valuable in the treatment of various diseases ranging from dermatosis to cancer, thereby emphasizing their important roles as therapeutic agents. The ability of As compounds, especially arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL), has fundamentally altered people's understanding of the poison, and has become a major factor in the re-emergence of Western medicine candidates to treat leukemia and other solid tumors. However, long-term exposure to As has been correlated with numerous disadvantageous influences on health, particularly carcinogenesis. Importantly, accumulating evidence suggests that biotransformation of As, as a step to eliminate As from the human body, can induce alterations at the genetic and epigenetic levels, resulting in therapeutic effects or carcinogenesis. In this article, we aimed to provide a systematic overview of the primary contributions associated with As and its compounds, as well as the detailed mechanisms applied in APL cells and carcinogenic toxicology. This review may help to understand the underlying mechanisms and safe wide clinical applications of medicinal As along with its compounds.


Subject(s)
Antineoplastic Agents/therapeutic use , Arsenicals/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Antineoplastic Agents/adverse effects , Arsenicals/adverse effects , Humans , Leukemia, Promyelocytic, Acute/metabolism
11.
Clin Pharmacokinet ; 60(5): 585-601, 2021 05.
Article in English | MEDLINE | ID: mdl-33723723

ABSTRACT

Drug metabolism is a critical process for the removal of unwanted substances from the body. In humans, approximately 80% of oxidative metabolism and almost 50% of the overall elimination of commonly used drugs can be attributed to one or more of various cytochrome P450 (CYP) enzymes from CYP families 1-3. In addition to the basic metabolic effects for elimination, CYP enzymes in vivo are capable of affecting the treatment outcomes in many cases. Drug-metabolizing CYP enzymes are mainly expressed in the liver and intestine, the two principal drug oxidation and elimination organs, where they can significantly influence the drug action, safety, and bioavailability by mediating phase I metabolism and first-pass metabolism. Furthermore, CYP-mediated local drug metabolism in the sites of action may also have the potential to impact drug response, according to the literature in recent years. This article underlines the ability of CYP enzymes to influence treatment outcomes by discussing CYP-mediated diversified drug metabolism in primary metabolic sites (liver and intestine) and typical action sites (brain and tumors) according to their expression levels and metabolic activity. Moreover, intrinsic and extrinsic factors of personal differential CYP phenotypes that contribute to interindividual variation of treatment outcomes are also reviewed to introduce the multifarious pivotal role of CYP-mediated metabolism and clearance in drug therapy.


Subject(s)
Cytochrome P-450 Enzyme System , Pharmaceutical Preparations , Humans , Liver , Microsomes, Liver , Treatment Outcome
12.
Pharmacol Res ; 165: 105371, 2021 03.
Article in English | MEDLINE | ID: mdl-33460792

ABSTRACT

Drug-induced nephrotoxicity is a frequent adverse event that contributes to acute kidney injury with tubular and/or glomerular lesions. Methotrexate (MTX) is a folate analog used against a myriad of malignancies and autoimmune diseases. Unfortunately, ambiguous renal toxicology limits its safe clinical usage. Based on our previous studies, 7-OH MTX as an overlooked oxidative metabolite of MTX was proposed to be the main culprit responsible for nephrotoxicity, while nobiletin, a naturally occurring polymethoxylated flavonoid screened from our prepared total phenolic extracts of Citrus aurantium L. (TPE-CA), was employed as a therapeutic agent for drug-drug interactions. According to the present study, nobiletin can ameliorate the renal accumulation of 7-OH MTX through the interaction with aldehyde oxidase. RNA-seq analysis revealed that 7-OH MTX was mainly related to protein processing in endoplasmic reticulum (ER) stress, with the PERK/CHOP pathway selected as the most significant for metabolic nephrotoxicity. Meanwhile, the cross-linked proteins and conducted signals were investigated by western blotting and further verified by GSK inhibition analyses. These results indicated that nobiletin protected renal function from MTX-induced nephrotoxicity by modulating metabolism and ameliorated the metabolic toxicity of 7-OH MTX on ER stress-induced PERK/CHOP conduction by maintaining Ca2+ homeostasis and reducing the production of reactive oxygen species.


Subject(s)
Acute Kidney Injury/chemically induced , Endoplasmic Reticulum Stress/drug effects , Methotrexate/analogs & derivatives , Methotrexate/toxicity , Signal Transduction/drug effects , Transcription Factor CHOP/metabolism , eIF-2 Kinase/metabolism , Acute Kidney Injury/pathology , Animals , Calcium/metabolism , Drug Interactions , Flavones , Flow Cytometry , Fluorescent Antibody Technique , Male , Methotrexate/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism
13.
J Adv Res ; 34: 137-147, 2021 12.
Article in English | MEDLINE | ID: mdl-35024186

ABSTRACT

Introduction: Endothelial damage (ED) has been implicated in accelerating the development of atherosclerosis. The latter condition is a risk factor for developing several cardiovascular diseases (CVDs) associated with high morbidity and mortality rates worldwide. Objectives: In our previous studies, we found naringenin (Nar), a bioactive flavanone compound, to protect against mitochondrial damage and oxidative stress. Though the pleiotropic effects of Nar have been well described, precise cytoprotective mechanisms of Nar against homocysteine (Hcy) induced ED remains elusive. Understanding these events may give an insight in to prevention and treatment of CVDs. Methods: After ruling out the NMDA-R1 mediated pathway, RNA-Seq, a novel transcriptomic technique uncovered AMPK signaling pathway was identified as the mechanism with which Nar corrects ED. Further in vivo and in vitro tests validated the role of Nar against ED. Results: In particular, Nar activates AMPKα/Sirt1 signaling pathway, which restores mitochondrial Ca2+ balance and ultimately lowered production of reactive oxygen species (ROS). Activated AMPKα/Sirt1 signaling pathway also up-regulates endothelial nitric oxide synthase (eNOS) activity, and then increasing the production of nitric oxide (NO), ultimately ameliorating ED. Conclusion: Nar could increase the ROS elimination and decrease eNOS uncoupling, subsequently upregulate the NO bioavailability and endothelial function by activating AMPKα/Sirt1 signaling pathway.


Subject(s)
Flavanones , Sirtuin 1 , AMP-Activated Protein Kinases/genetics , Flavanones/pharmacology , Homocysteine , Sirtuin 1/genetics
14.
Int J Nanomedicine ; 15: 8369-8382, 2020.
Article in English | MEDLINE | ID: mdl-33149581

ABSTRACT

INTRODUCTION: Auraptene (AUR), a natural bioactive prenyloxy coumarin, is a highly pleiotropic molecule that can bind to the MT1 receptor and can effectively reduce the proliferation and migration of breast cancer cells. Cisplatin (CDDP), as the first synthetic platinum-based anticancer drug, is widely used in the clinic due to its definite mechanism and therapeutic effect on diverse tumors. However, both of AUR and CDDP exhibit some disadvantages when used alone, including poor solubility, low bioavailability, lack of selectivity and systemic toxicity when they are used singly. METHODS: Therefore, the biodegradable materials hyaluronic acid (HA) and ß-cyclodextrin derivative (mono-(6-amino-mono-6-deoxy)-ß-CD, CD) were employed as carriers to load AUR and CDDP to form nanogel (CDDPHA-CD@AUR) capable of dual-targeted delivery and synergistic therapy for breast cancer and cell imaging. RESULTS: With the help of the CDDP-crosslinked CD-loaded structure, the newly synthesized nanogel exhibited excellent physiological stability and fluorescence effects. The release of AUR and CDDP was affected by the pH value, which was beneficial to the selective release in the tumor microenvironment. Cell experiments in vitro demonstrated that the nanogel could be selectively internalized by MCF-7 cells and exhibited low cytotoxicity to HK-2 cells. Antitumor experiments in vivo showed that the nanogel have better antitumor effects and lower systemic toxicity. CONCLUSION: Based on these, the nanogel loaded with AUR and CDDP have the potential for targeted delivery against breast cancer.


Subject(s)
Breast Neoplasms/drug therapy , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Coumarins/administration & dosage , Coumarins/therapeutic use , Nanogels/chemistry , Animals , Breast Neoplasms/pathology , Cell Death , Drug Carriers/chemistry , Drug Liberation , Endocytosis , Female , Hemolysis , Humans , Hyaluronic Acid/chemistry , Hydrogen-Ion Concentration , MCF-7 Cells , Mice, Inbred BALB C , Mice, Nude , Nanogels/ultrastructure , Organ Specificity , Particle Size , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Rabbits , Spectrometry, Fluorescence , Spectroscopy, Fourier Transform Infrared
15.
Int J Biol Macromol ; 165(Pt A): 1264-1275, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33039536

ABSTRACT

Hyaluronic acid (HA) is a multifunctional high molecular weight polysaccharide produced by synoviocytes, fibroblasts, and chondrocytes, and is naturally found in many tissues and fluids, and more abundantly in articular cartilage and synovial fluid. Naturally occurring HA is thought to participate in many biological processes, such as regulation of cell adhesion and cell motility, manipulation of cell differentiation and proliferation, and providing mechanical properties to tissues (Girish and Kemparaju, 2007). Due to its excellent physicochemical properties such as high viscosity, elasticity, biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity, HA based formulations have a wide range of applications and serves as a promising rejuvenating biomacromolecule in biomedical applications. In recent decades, HA is currently a popular topic, and has been widely used in bone related diseases for its remarkable efficacy in articular cartilage lubrication, analgesia, anti-inflammation, immunomodulatory, chondroprotection, anti-cancer and etc. Moreover, the safety and tolerability of HA based formulations have also been well-documented for treatment of various types of bone related diseases (Chen et al., 2018). This review gives a deep understanding on the special benefits and provides a mechanism-based rationale for the use of HA in bone related diseases conditions with special reference to osteoarthritis (OA), rheumatoid arthritis (RA), bone metastatic cancers.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Bone Diseases/drug therapy , Hyaluronic Acid/therapeutic use , Osteoarthritis/drug therapy , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/pathology , Bone Diseases/pathology , Cartilage, Articular/drug effects , Cartilage, Articular/growth & development , Cell Differentiation/drug effects , Chondrocytes/drug effects , Humans , Hyaluronic Acid/chemistry , Osteoarthritis/pathology , Rejuvenation/physiology
16.
Cell Death Dis ; 11(9): 797, 2020 09 24.
Article in English | MEDLINE | ID: mdl-32973135

ABSTRACT

Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3ß), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.


Subject(s)
Drug Resistance, Multiple/genetics , Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Cell Proliferation , Humans , Neoplasms/drug therapy , Signal Transduction
17.
Front Pharmacol ; 11: 605823, 2020.
Article in English | MEDLINE | ID: mdl-33505311

ABSTRACT

Aflatoxins (AFs) are commonly contaminating mycotoxins in foods and medicinal materials. Since they were first discovered to cause "turkey X" disease in the United Kingdom in the early 1960s, the extreme toxicity of AFs in the human liver received serious attention. The liver is the major target organ where AFs are metabolized and converted into extremely toxic forms to engender hepatotoxicity. AFs influence mitochondrial respiratory function and destroy normal mitochondrial structure. AFs initiate damage to mitochondria and subsequent oxidative stress. AFs block cellular survival pathways, such as autophagy that eliminates impaired cellular structures and the antioxidant system that copes with oxidative stress, which may underlie their high toxicities. AFs induce cell death via intrinsic and extrinsic apoptosis pathways and influence the cell cycle and growth via microribonucleic acids (miRNAs). Furthermore, AFs induce the hepatic local inflammatory microenvironment to exacerbate hepatotoxicity via upregulation of NF-κB signaling pathway and inflammasome assembly in the presence of Kupffer cells (liver innate immunocytes). This review addresses the mechanisms of AFs-induced hepatotoxicity from various aspects and provides background knowledge to better understand AFs-related hepatoxic diseases.

18.
Artif Cells Nanomed Biotechnol ; 47(1): 4222-4233, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31713452

ABSTRACT

Gold nanoparticles (AuNPs), as a kind of inorganic nanoparticle, have been gradually recognized as one of the most promising nanomaterials, which is attributed to their unique optical, electronic, sensing and biochemical characteristics. Due to such unique characteristics, AuNPs have been widely applied in biomedical fields such as diagnosis, biosensing and drug delivery. Except for their use in cancer treatment alone with their photothermal ablation of solid tumours, when used with anticancer drugs, AuNPs can exert a dual role in treating cancer. With the advantages of protecting drugs from degradation and leakage in the physiological environment, tuneable modification in size, surface and shape, and biocompatibility, AuNPs can be used as promising drug carriers in anticancer drug design. However, there are still many aspects that need to be improved during the usage of drug carriers in pharmacology including the following aspects: prolongation in the plasma, enhancement in targeting accumulation, improvement in cellular uptake and the control of intracellular release. AuNPs are important drug carriers.


Subject(s)
Drug Carriers/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Drug Carriers/metabolism , Gold/metabolism , Humans , Ligands
19.
Biomed Pharmacother ; 118: 109340, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31545284

ABSTRACT

It is necessary to design a reasonable drug delivery system(DDS) for targeted release to overcome the potential toxicity and poor selectivity of anti-tumor drug. How a drug is released from a DDS is a critical issue that determines whether the DDS is designed successfully. We all know that the microenvironment of tumors is quite different from normal tissues, such as its acidic environment, different expression levels of some enzymes, etc. These features are widely used in the design of DDSs and play an important role in the drug release process in vivo. Numerous DDSs have been designed and synthesized. This article attention to how drugs are released from DDSs. We summarizes and classify the characteristic enzymes and chemical bonds used in the drug release process by browsing a large number of papers, and describes how they are applied in DDSs with specific examples. By understanding these acid-sensitive chemical bonds and over-expressed enzymes in tumors, different DDSs can be designed for different drug structures to solve specific problems of anti-tumor drugs.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Delivery Systems , Drug Liberation , Hydrogen-Ion Concentration , Hydrolysis , Peptides/chemistry
20.
Sci Total Environ ; 693: 133393, 2019 Nov 25.
Article in English | MEDLINE | ID: mdl-31374496

ABSTRACT

Black runoff occasionally flows from cutover areas of Eucalyptus plantations, polluting rivers and ponds, and resulting in fish death in severe cases. However, the occurrence patterns and environmental impacts of this black water remain unclear. Herein, we analyzed the major characteristics of black water at the occurrence sites, tested the complexation reaction of ground eucalyptus leaves with a solution of Fe3+, and determined the color and absorbance of the complex solution. The results showed that the water was dark blue, with weak acidity and strong light absorbance. The water contained a high level of dissolved organic matter content, while its chemical oxygen demand, total N, total P, NO3--N, and NH4+-N concentrations were significantly higher than those in the stream water from Eucalyptus, Pinus massoniana Lamb., and Cunninghamia lanceolata stands during the growth period. Additionally, the tannic acid concentration in the black water was 1.0 mg L-1 higher than that in the stream water from the Eucalyptus stand. The input of black water increases the concentration of tannic acid and NH4+-N, and the degradation of organic matter consumes dissolved oxygen in downstream ponds, leading to fish deaths. The presence of fresh logging residues and hot, humid weather also enable black water formation. Field investigations and simulation experiments revealed fresh Eucalyptus residues decompose rapidly under high-temperature and rainfall conditions, releasing large amounts of tannic acid, which reacts with Fe3+ to form a dark blue tannic acid­iron complex and results in black water. These results indicate that the rich Fe3+ in runoff may be a key factor in the occurrence of black water. The logging of Eucalyptus plantations during the dry season or on non-rainy days and a reduction in the logging area could prevent the occurrence of black water or mitigate the extent of its environmental hazards.


Subject(s)
Eucalyptus , Fishes/physiology , Forestry/methods , Ponds/chemistry , Water/chemistry , Animals , China , Climate , Environment , Water Quality
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