E. Brown, T. McKee, E. Ditomaso et al.
Hasil untuk "Therapeutics. Pharmacology"
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K. Roth, Isa Mambetsariev, Prakash Kulkarni et al.
Mitochondria have emerged as important pharmacological targets because of their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis. Furthermore, mitochondria can engage in crosstalk with the tumor microenvironment, and signals from cancer-associated fibroblasts can impinge on mitochondria. Cancer cells can also acquire a hybrid phenotype in which both glycolysis and oxidative phosphorylation (OXPHOS) can be utilized. This hybrid phenotype can facilitate metabolic plasticity of cancer cells more specifically in metastasis and therapy-resistance. In light of the metabolic heterogeneity and plasticity of cancer cells that had until recently remained unappreciated, strategies targeting cancer metabolic dependency appear to be promising in the development of novel and effective cancer therapeutics.
Karl Hazel, A. O’Connor
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, a relapsing and remitting clinical course, requirement for lifelong medication and often, significant morbidity. While multiple effective therapeutic options exist for the treatment of IBD, a proportion of patients will either fail to respond or lose response to therapy. Advances in therapeutics, such as the gut-specific anti-integrins, now offer patients an alternative option to systemic immunosuppression. Anti-interleukin 12 (anti-IL-12)/IL-23 agents offer new and effective treatment options for CD, while the oral small molecules now offer an oral alternative for the treatment of moderate-to-severe disease, previously requiring subcutaneous injection or intravenous infusion. Alternatives to pharmacological treatment such as stem-cell transplant and faecal microbiota transplant are also showing some promise in the treatment of both CD and UC.
Ahmed O. Elzoghby, Mona A. Abdelmoneem, Islam A Hassanin et al.
Recent progress in protein-based nanomedicine, inspired by the success of Abraxane® albumin-paclitaxel nanoparticles, have resulted in novel therapeutics used for treatment of challenging diseases like cancer and viral infections. However, absence of specific drug targeting, poor pharmacokinetics, premature drug release, and off-target toxicity are still formidable challenges in the clinic. Therefore, alternative protein-based nanomedicines were developed to overcome those challenges. In this regard, lactoferrin (Lf), a glycoprotein of transferrin family, offers a promising biodegradable well tolerated material that could be exploited both as an active therapeutic and drug nanocarrier. This review highlights the major pharmacological actions of Lf including anti-cancer, antiviral, and immunomodulatory actions. Delivery technologies of Lf to improve its pries and enhance its efficacy were also reviewed. Moreover, different nano-engineering strategies used for fabrication of drug-loaded Lf nanocarriers were discussed. In addition, the use of Lf for functionalization of drug nanocarriers with emphasis on tumor-targeted drug delivery was illustrated. Besides its wide application in oncology nano-therapeutics, we discussed the recent advances of Lf-based nanocarriers as efficient platforms for delivery of anti-parkinsonian, anti-Alzheimer, anti-viral drugs, immunomodulatory and bone engineering applications.
Xiaowei Cui, Shiyuan Wang, Hui Cao et al.
Traditional Chinese Medicine (TCM) has been widely used in China and is regarded as the most important therapeutic. Polygonatum sibiricum (PS), a natural plant used in traditional Chinese medicine, has various functions associated with a number of its components. There are many compositions in PS including polysaccharides, steroids, anthraquinone, alkaloids, cardiac glycosides, lignin, vitamins, various acids, and so on. Of these, polysaccharides play a significant role in PS-based therapeutics. This article summarizes Polygonatum sibiricum polysaccharides (PSP) have many pharmacological applications and biological activities, such as their antioxidant activity, anti-aging activity, an anti-fatigue effect, immunity enhancement effect, antibacterial effect, anti-inflammatory effect, hypolipidemic and antiatherosclerotic effects, anti-osteoporosis effect, liver protection, treatment of diabetes mellitus (DM), anti-cancer effect, and may help prevent Alzheimer’s disease, and so on. This review summarized the extraction method, purification method, compositions, pharmacological applications, biological activities, biosynthesis, and prospects of PSP, providing a basis for further study of PS and PSP.
Hossein Derakhshandeh, Fariba Aghabaglou, A. McCarthy et al.
Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re‐epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.
M. Ansari, F. Khan, Haaris Ahsan Safdari et al.
In the past decades, the branch of complementary and alternative medicine based therapeutics has gained considerable attention worldwide. Pharmacological efficacy of various traditional medicinal plants, their products and/or product derivatives have been explored on an increasing scale. Tanshinone IIA (Tan IIA) is a pharmacologically active lipophilic component of Salvia miltiorrhiza extract. Tan IIA shares a history of high repute in Traditional Chinese Medicine. Reckoning with these, the present review collates the pharmacological properties of Tan IIA with a special emphasis on its therapeutic potential against diverse diseases including cardiovascular diseases, cerebrovascular diseases, cancer, diabetes, obesity and neurogenerative diseases. Further, possible applications of various therapeutic preparations of Tan IIA were discussed with special emphasis on nano-based drug delivery formulations. Considering the tremendous advancement in the field of nanomedicine and the therapeutic potential of Tan IIA, the convergence of these two aspects can be foreseen with great promise in clinical application.
Kanika Khanna, S. Kohli, R. Kaur et al.
Current scenario depicts that world has been clenched by COVID-19 pandemic. Inevitably, public health and safety measures could be undertaken in order to dwindle the infection threat and mortality. Moreover, to overcome the global menace and drawing out world from moribund stage, there is an exigency for social distancing and quarantines. Since December, 2019, coronavirus, SARS-CoV-2 (COVID-19) have came into existence and up till now world is still in the state of shock.At this point of time, COVID-19 has entered perilous phase, creating havoc among individuals, and this has been directly implied due to enhanced globalisation and ability of the virus to acclimatize at all conditions. The unabated transmission is due to lack of drugs, vaccines and therapeutics against this viral outbreak. But research is still underway to formulate the vaccines or drugs by this means, as scientific communities are continuously working to unravel the pharmacologically active compounds that might offer a new insight for curbing infections and pandemics. Therefore, the topical COVID-19 situation highlights an immediate need for effective therapeutics against SARS-CoV-2. Towards this effort, the present review discusses the vital concepts related to COVID-19, in terms of its origin, transmission, clinical aspects and diagnosis. However, here, we have formulated the novel concept hitherto, ancient means of traditional medicines or herbal plants to beat this pandemic.
Fengzhang Wang, Yong Xue, Lin Fu et al.
Abstract Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a well-known vanilloid, which is the main spicy component in chili peppers, showing several biological activities and the potential applications range from food flavorings to therapeutics. Traditional extraction of capsaicin by organic solvents was time-consuming, some new methods such as aqueous two-phase method and ionic liquid extraction method have been developed. During past few decades, an ample variety of biological effects of capsaicin have been evaluated. Capsaicin can be used in biofilms and antifouling coatings due to its antimicrobial activity, allowing it has a promising application in food packaging, food preservation, marine environment and dental therapy. Capsaicin also play a crucial role in metabolic disorders, including weight loss, pressure lowing and insulin reduction effects. In addition, capsaicin was identified effective on preventing human cancers, such as lung cancer, stomach cancer, colon cancer and breast cancer by inducing apoptosis and inhibiting cell proliferation of tumor cells. Previous research also suggest the positive effects of capsaicin on pain relief and cognitive impairment. Capsaicin, the agonist of transient receptor potential vanilloid type 1 (TRPV1), could selectively activate TRPV1, inducing Ca2+ influx and related signaling pathways. Recently, gut microbiota was also involved in some diseases therapeutics, but its influence on the effects of capsaicin still need to be deeply studied. In this review, different extraction and purification methods of capsaicin, its biological activities and pharmacological effects were systematically summarized, as well as the possible mechanisms were also deeply discussed. This article will give an updated and better understanding of capsaicin-related biological effects and provide theoretical basis for its further research and applications in human health and manufacture development.
Seiji Ogawa, Kuniaki Ota, Kaori Nishizawa et al.
Oxidative stress (OS) affects men’s health and impairs spermatogenesis. Micronutrient antioxidants are available for male infertility as complemental support; however, their efficacy remains debatable. This study aimed to investigate whether antioxidants can help to reduce sperm OS and improve semen analysis and quality. We included 171 male partners of couples planning to undergo assisted reproductive technology (ART). Male partners, aged 29–41 years, of couples intending to conceive were self-selected to take daily antioxidants (n = 84) containing folic acid and zinc, or not to take antioxidants (n = 52) for 6 months. We analyzed the alterations in serum oxidant levels, sperm parameters, OS, and deoxyribonucleic acid fragmentation after 3 and 6 months. Additionally, implantation, clinical pregnancy, and miscarriage rates after vitrified–warmed embryo transfer were compared between those taking antioxidants and those not taking them after 6 months. In men with high static oxidation–reduction potential (sORP), we observed a significant improvement in sperm concentration and sORP. The high-quality blastocyst rate tended to increase, and implantation and clinical pregnancy rates also significantly increased after 6 months of intervention. The micronutrient antioxidants could improve sperm function by reducing OS and improving ART outcomes. Therefore, micronutrient antioxidants may be a viable treatment option for male infertility.
Min-Jia Hsieh, Ping-Hsing Tsai, Pin-Hsuan Chiang et al.
Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.
Kenan Çadırcı, Adil Furkan Kılıç, Muharrem Bayrak
Introduction:Helicobacter pylori (Hp)infection is widespread in the world.Hp can lead to chronic gastritis, chronic inflammation, and immune response.Immune cytokines, adipokines that occur with an immune response have been associated with insulin resistance, and obesity has been associated with 25-hydroxy vitamin D deficiency.Our study aimed to show the significant relationship between Hp positivity and 25-hydroxy vitamin D deficiency in obese individuals.Materials and Methods:Patients over the age of 20 who applied to the internal medicine department with dyspeptic complaints between January 1, 2019, and December 31, 2019, were divided into three groups as 18-24.9 (normal weight), 25-29.9 (overweight), 30-39.9 (obese) according to their body mass indexes (BMI).Urea breath test for Hp infection, 25-hydroxyvitamin D and other biochemical parameters, anthropometric measurements, education levels, systemic diseases, smoking history of patients who did not use proton pump inhibitor, and 25-hydroxyvitamin D for the last six months were retrospectively analyzed from the patient file archive.Results:The study was carried out with 632 cases, 51.6% (n = 326) of the patients were male, and 48.4% (n = 306) were female.The ages of the cases ranged from 21 to 65, and the mean age was 43.97 ± 12.87 years.Body mass index measurements of the cases included in the study ranged between 18.8 and 39.9 kg/m2, with a mean of 28.02 ± 4.98 kg/m2; %31.3% (n = 198) were normal weight, 35.5% (n = 224) were overweight and 33.2% (n = 210) were obese.A statistically significant difference was found between the Hp incidence rates according to the body mass index levels of the groups(p=0.001; p
Okim Okim Nsor, Babatunde Adebola Alabi, Babatunde Adebola Alabi et al.
IntroductionDespite the high phenolic content of Annona muricata, little is known about its anti-hypertensive and antihyperlipidemic properties. This study evaluated the anti-hypertensive and antihyperlipidemic potential of A. muricata leaf extracts.Materials and methodsForty-two male Wistar rats were divided into seven groups of six animals each. N-nitro-L-arginine methyl ester (L-NAME) was used to induce hypertension and hyperlipidemia.ResultsPhytochemical screening of Annona muricata leaf extracts (AMLE) revealed the presence of saponins, alkaloids, flavonoids, tannins, coumarins, steroids, terpenoids, and phenols. Comparing the methanol extract with the ethyl acetate fraction, quantification revealed that the methanol extract contained more phenolics, flavonoids, and alkaloids. The AMLE rats significantly reduced triglycerides, total cholesterol, LDL, VLDL, atherogenic index, coronary risk index, and blood pressure. The significant decrease in GSH, catalase, SOD, GST, and oxidative stress markers (MDA, nitrites, and MPO) was reversed by AMLE in a dose-dependent manner. Also, the elevated serum levels of TNF-α and IL-1β in the hypertensive rats were attenuated in the treatment groups.DiscussionThis study suggests the potential ameliorative effects of Annona muricata leaf extracts against L-NAME-induced hypertension in rats. Notably, the study showed the antioxidant and anti-inflammatory properties of A. muricata leaf extracts, which is seen in its ability to attenuate oxidative stress and inflammatory cytokines in L-NAME-induced hypertensive rats. A. muricata extracts also decreased atherogenic risk and improved lipid profiles.
L. Slosky, Yushi Bai, K. Toth et al.
Small molecule neurotensin receptor 1 (NTSR1) agonists have been pursued for more than 40 years as potential therapeutics for psychiatric disorders, including drug addiction. Clinical development of NTSR1 agonists has, however, been precluded by their severe side effects. NTSR1, a G protein-coupled receptor (GPCR), signals through the canonical activation of G proteins and engages β-arrestins to mediate distinct cellular signaling events. Here, we characterize the allosteric NTSR1 modulator SBI-553. This small molecule not only acts as a β-arrestin-biased agonist but also extends profound β-arrestin bias to the endogenous ligand by selectively antagonizing G protein signaling. SBI-553 shows efficacy in animal models of psychostimulant abuse, including cocaine self-administration, without the side effects characteristic of balanced NTSR1 agonism. These findings indicate that NTSR1 G protein and β-arrestin activation produce discrete and separable physiological effects, thus providing a strategy to develop safer GPCR-targeting therapeutics with more directed pharmacological action.
Cheorl-Ho Kim, Michael Heinrich, Michael Heinrich et al.
Huangming Zhuang, Xunshan Ren, Fuze Jiang et al.
Abstract Background Osteoarthritis (OA) is a common chronic disease characterized by chronic inflammation and extracellular matrix degradation. Indole-3-propionic acid (IPA) is a tryptophan metabolite secreted by intestinal flora, which can exert anti-inflammatory effects in a variety of diseases. In this study, we further investigated the potential therapeutic role of IPA in OA and the underlying mechanism. Methods IL-1β was utilized to induce chondrocyte inflammation. Then, the cytotoxicity of IPA on rat chondrocytes was assessed. Meanwhile, RT-qPCR, Griess reaction, ELISA, Western blot and immunofluorescence were performed to evaluate the expression of inflammatory factors and stromal proteins, and the NF-κB pathway in chondrocytes treated with IL-1β alone, with IPA or with aryl hydrocarbon receptor (AhR) knockdown. An OA rat model was established by anterior cruciate ligament transection, and hematoxylin-eosin staining, Safranin-O/Fast Green staining and immunochemistry were applied to estimate OA severity. Results IPA did not affect cellular viability at concentrations up to 80 µM. IPA significantly inhibited the IL-1β-induced expression of inflammatory factors (Nitric oxide, PGE2, TNF-α, IL-6, iNOS and COX-2) and matrix-degrading enzymes (MMP-3, MMP-13 and ADAMTS-5), upregulated the expression of anabolic markers (aggrecan and collagen-II) and inactivated the NF-κB pathway. However, AhR knockdown could abolish the above protection capabilities and the suppression of the NF-κB pathway induced by IPA. Furthermore, IPA significantly reduced serum inflammatory cytokines expression, cartilage destruction and synovitis in vivo, demonstrating its protective role in OA progression. Conclusion IPA improved IL-1β-induced chondrocyte inflammation and extracellular matrix degradation through the AhR/NF-κB axis, which provides an innovative therapeutic strategy for OA.
Zhuoying Liu, Yixuan Zhang, Ji Youn Youn et al.
The prevalent use of electronic cigarettes (e-cigarettes) has increased exponentially in recent years, especially in youth who are attracted to flavored e-cigarettes. Indeed, e-cigarette or vaping product use-associated lung injury (EVALI) cases started to emerge in the United States in August 2019, resulting in 2807 hospitalized cases and 68 deaths as of 18 February 2020. In the present study, we investigated, for the first time, whether flavored and nicotine containing e-cigarettes induce endothelial dysfunction to result in impaired angiogenesis and wound healing particularly under diabetic condition. Nicotine containing e-cigarettes with various contents of nicotine (0, 1.2%, 2.4%), and flavored e-cigarettes of classic tobacco, mint, menthol, and vanilla or fruit from BLU (nicotine 2.4%) or JUUL (nicotine 3%), were used to treat endothelial cells in vitro and streptozotocin-induced diabetic mice in vivo. Endothelial cell superoxide production, determined by dihydroethidium (DHE) fluorescent imaging and electron spin resonance (ESR), was markedly increased by exposure to e-cigarette extract (e-CSE) in a nicotine-content dependent manner, while nitric oxide (NO) bioavailability detected by DAF-FM fluorescent imaging was substantially decreased. All of the different flavored e-cigarettes examined also showed significant effects in increasing superoxide production while diminishing NO bioavailability. Endothelial cell apoptosis evaluated by caspase 3 activity was markedly increased by exposure to e-CSE prepared from flavored and nicotine containing e-cigarettes. Endothelial monolayer wound assays revealed that nicotine-containing and flavored e-cigarettes induced impaired angiogenic wound repair of endothelial cell monolayers. Furthermore, vascular endothelial growth factor (VEGF) stimulated wound healing in diabetic mice was impaired by exposure to e-CSEs prepared from nicotine-containing and flavored e-cigarettes. Taken together, our data demonstrate for the first time that flavored and nicotine-containing e-cigarettes induce endothelial dysfunction through excessive ROS production, resulting in decreased NO bioavailability, increased endothelial cell apoptosis, and impairment in angiogenesis and wound healing, especially under diabetic condition. These responses of endothelial dysfunction likely underlie harmful effects of e-cigarettes in endothelial-rich organs, such as heart and lungs. These data also indicate that rigorous regulation on e-cigarette use should be enforced in diabetic and/or surgical patients to avoid severe consequences from impaired angiogenesis/wound healing.
Camelia Cristina Vlad, Bogdan Păcularu-Burada, Aida Mihaela Vasile et al.
Emerging customized designs to upgrade the functional potential of freeze-dried apple pomace was used in this study, in order to transform the industrial by-products into ingredients containing probiotics, for a better and healthier food composition. The freeze-dried apple pomace was analyzed for free and bounded phenolic contents, highlighting a significant level of caffeic acid (4978.00 ± 900.00 mg/100 g dry matter (DM)), trans-cinnamic acid (2144.20 ± 37.60 mg/100 g DM) and quercetin 3-β-D-glucoside (236.60 ± 3.12 mg/100 g DM). The pectin extraction yield was approximatively 24%, with a degree of esterification of 37.68 ± 1.74%, and a methoxyl content of 5.58 ± 0.88%. The freeze-dried apple pomace was added in a different ratio as a supplement to cultural medium of <i>Loigolactobacillus bifermentans</i> MIUG BL 16, suggesting a significant prebiotic effect (<i>p</i> < 0.05) at concentration between 1% and 2%. The apple pomace was used to design three freeze-dried ingredients containing probiotic, with a high level of polyphenolic content (6.38 ± 0.14 mg gallic acid equivalents/g DM) and antioxidant activity (42.25 ± 4.58 mMol Trolox/g DM) for the powder containing apple pomace ethanolic extract. When inulin was used as a prebiotic adjuvant, the obtained powder showed a 6 log/g DM viable cell count. The ingredients were added to fermented vegetable soy milk-based products, allowing us to improve the polyphenolic content, antioxidant activity and viable cell counts. The approach designed in this study allowed us to obtain ingredients suitable to add value to food, whereas premises to align with the current circular economy premises, by reintegrating the industrial waste as sources of high added value compounds, are also provided.
Ran Zhu, Wei-yi Qi, Ting-wei Liu et al.
Acute pulmonary embolism (APE) is a disabling diseases with high incidence rate and mortality rate. Although with high specificity, D-Dimer lacks specificity to assess APE, hence additional diagnostic and prognostic biomarkers are necessary. APE is widely treated with serine protease urokinase or urokinase-type plasminogen activator (uPA), which act as a catalyst for conversion of plasminogen to plasmin to resolve blood clots. However, it is unknown the role of differential expression of microRNAs (miRNAs) in protective effect of uPA against APE. Hence, we performed miRNA profiling in a hypoxia/reoxygenation (H/R) model of bronchial epithelial BEAS-2B cells in vitro and a APE mice model in vivo. Our analysis revealed that miR-34a-5p, miR-324-5p, miR-331-3p are upregulated with H/R or APE induction, whereas miR-429, miR-491-5p, and miR-449a are downregulated. The differential expression of the miRNAs was attenuated to levels comparable to control by treatment with uPA both in vitro and in vivo. In situ target prediction and analysis of potential functions of the target genes showed that the enrichment of biological processes and pathways were related to cell growth, proliferation, and inflammation. Ectopic overexpression of miR-449a using a mimic completely attenuated the protective effect of uPA in the H/R model in vitro. These results provide a group of miRNAs that could be used as markers, and the modulation of these miRNAs might have potential therapeutic benefits in patients with APE, which need to be validated in additional studies in humans.
Zhuo Liu, Dongxin Wang, Qian Cao et al.
Colorectal cancer (CRC) is a worldwide disease posing serious threats to people’s life. Surgery and postsurgical chemotherapy are still the first choices to control the rapid progression of cancer. However, tumor recurrence and even distant metastasis are prone to occur. As a result, it is in urgent demand to find a new method to control CRC progression while inhibiting distant metastasis. On this basis, this study developed the three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials. The Chinese traditional drugs 20 (S)-ginsenoside Rg3 (Rg3) and chemotherapeutic agent 5-fluorouracil (5-Fu) were loaded in the inner hydrogel and middle fibrous membrane and could be constantly released at the same time and space. The outer hydrogel was decorated with phenylboronic acid (PA) to interact with sialic acid expressed on the CRC cell surface. The composite materials possessed biocompatibility and showed no toxicity to normal human intestinal mucosa endothelial cells HIEC. According to the results, the cell viability of CT26 could be significantly decreased in vitro. The three-layered functionalized materials inhibited the original tumor progression and distant tumor metastasis to the liver in an orthotopic colon cancer mouse model by increasing the caspase3 expression and inhibiting the expressions of Bcl-2, Ki-67, and VEGF. In addition, the functions of major organs were not significantly damaged. Our study provides a safe and efficacious method of this three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials for CRC treatment.
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