Transdermal drug delivery (TDD) has recently emerged as an effective alternative to oral and injection administration because of its less invasiveness, low rejection rate, and excellent ease of ...administration. TDD has made an important contribution to medical practice such as diabetes, hemorrhoids, arthritis, migraine, and schizophrenia treatment, but has yet to fully achieve its potential in the treatment of obesity. Obesity has reached epidemic proportions globally and posed a significant threat to human health. Various approaches, including oral and injection administration have widely been used in clinical setting for obesity treatment. However, these traditional options remain ineffective and inconvenient, and carry risks of adverse effects. Therefore, alternative and advanced drug delivery strategies with higher efficacy and less toxicity such as TDD are urgently required for obesity treatment. This review summarizes current TDD technology, and the main anti-obesity drug delivery system. This review also provides insights into various anti-obesity drugs under study with a focus on the recent developments of TDD system for enhanced anti-obesity drug delivery. Although most of presented studies stay in animal stage, the application of TDD in anti-obesity drugs would have a significant impact on bringing safe and effective therapies to obese patients in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mucin2 (Muc2) is the main component of the intestinal mucosal layer and is highly expressed in mucous colorectal cancer. Previous studies conducted by our lab found that the recombinant protein ...Amuc_1434 (expressed in
prokaryote cell system, hereinafter termed Amuc_1434*), derived from
, can degrade Muc2. Thus, the main objective of this study was to explore the effects of Amuc_1434* on LS174T in colorectal cancer cells expressing Muc2. Results from this study demonstrated that Amuc_1434* inhibited the proliferation of LS174T cells, which was related to its ability to degrade Muc2. Amuc_1434* also blocked the G0/G1 phase of the cell cycle of LS174T cells and upregulated the expression of tumor protein 53 (p53), which is a cell cycle-related protein. In addition, Amuc_1434* promoted apoptosis of LS174T cells and increased mitochondrial ROS levels in LS174T cells. The mitochondrial membrane potential of LS174T cells was also downregulated by Amuc_1434*. Amuc_1434* can activate the death receptor pathway and mitochondrial pathway of apoptosis by upregulating tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). In conclusion, our study was the first to demonstrate that the protein Amuc_1434* derived from
suppresses LS174T cell viability via TRAIL-mediated apoptosis pathway.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Influenza A is an acute respiratory infectious disease caused by the influenza A virus, which seriously threatens global human health and causes substantial economic losses every year. With the ...emergence of new viral strains, anti-influenza drugs remain the most effective treatment for influenza A. Research on traditional, innovative small-molecule drugs faces many challenges, while computer-aided drug design (CADD) offers opportunities for the rapid and effective development of innovative drugs. This literature review describes the general process of CADD, the viral proteins that play an essential role in the life cycle of the influenza A virus and can be used as therapeutic targets for anti-influenza drugs, and examples of drug screening of viral target proteins by applying the CADD approach. Finally, the main limitations of current CADD strategies in anti-influenza drug discovery and the field's future directions are discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
This study aimed to investigate the role of lncRNA miR143HG in laryngeal squamous cell carcinoma (LSCC).
Methods
Quantitative polymerase chain reaction (PCR) and paired t test were used to ...measure and compare expression levels of miR143HG and miR‐21 in LSCC and nontumor tissues. To analyze the interactions between miR143HG and miR‐21, UM‐SCC‐17A cells were transfected miR143HG expression vector or miR‐21 mimic. The effects of miR143HG and miR‐21 overexpression on UM‐SCC‐17A cell invasion and migration were analyzed by transwell assays.
Results
We found that miR143HG was downregulated in LSCC and inversely correlated with miR‐21. In LSCC cells, miR143HG overexpression led to the downregulated expression of miR‐21, whereas miR‐21 overexpression failed to affect miR143HG. Methylation‐specific PCR results showed that miR143HG overexpression led to increased methylation of miR‐21. Low expression levels of miR143HG were correlated with poor survival. Overexpression of miR143HG led to decreased, whereas miR‐21 overexpression resulted in increased rate of LSCC cell migration and invasion. In addition, miR‐21 overexpression led to reduced effects of miR143HG on cell invasion and migration.
Conclusion
Therefore, miR143HG suppresses miR‐21 via methylation to regulate cell behaviors in LSCC.
Level of Evidence
NA Laryngoscope, 130:E640–E645, 2020
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract In spite of significant advantages exhibiting in the applications of silicon dioxide particles in biological and medicine fields, their adverse effects still remain a big concern. Herein ...monodisperse spherical SiO2 particles with diameters of 80 nm and 500 nm were used to study their interactions with human dermal fibroblasts. Both the particles were readily internalized into the fibroblasts within a short time. The 500 nm particles were taken up in a larger amount through macropinocytosis and clathrin-mediated endocytosis pathways, whereas uptake of the 80 nm SiO2 particles was mediated corporately by macropinocytosis, clathrin-mediated and caveolae-mediated endocytosis. The particles mainly dispersed in the cytoplasm or resided within the lysosomal vesicles, but could not enter into the cell nucleus within 24 h culture in vitro. Treatment with the 80 nm SiO2 particles caused apparently decrease of cell viability and also weakened the mitochondrial membrane potential. Further experiments demonstrated that the cell adhesion and migration were greatly affected by uptake of the SiO2 particles regardless of their size. RT-PCR results indicated down regulation of the mRNA expression of adhesion relevant genes, i.e. fibronectin, laminin and focal adhesion kinase (FAK).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Numerous studies have demonstrated that both smoking and diabetes are risk factors for mortality and caused-specific cardiovascular events. However, few studies systematically ...investigated to what extent the excess risk could be attributed to smoking among diabetic patients. Methods Literature references were searched up to April 2011 in MEDLINE and EMBASE, supplemented by manual searches. Inclusion criteria were prospective cohort studies, assessment of the association between smoking and total mortality, cardiovascular death, incidence of coronary heart disease (CHD), stroke and myocardial infarction (MI) in diabetic patients. Results Of 3758 studies in the literature searched, 46 were eligible with approximately 130,000 diabetic patients. The relative risk (RR) comparing smokers with nonsmokers was 1.4895% confidential interval (CI): 1.34–1.64 for total mortality (27 studies), 1.36(1.22–1.52) for cardiovascular mortality (9 studies), 1.54(1.31–1.82) for CHD (13 studies), 1.44(1.28–1.61) for stroke (9 studies) and 1.52(1.25–1.83) for MI (7 studies). Furthermore, the excess risk was observed among former and current smokers with a greater risk in current smokers. Subgroup analysis showed that the increased risk appeared to be consistent regardless of several study characteristics with the RRs ranging from 1.31 to 1.94 for all-cause mortality, 1.37 to 2.28 for CHD, 1.21 to 1.87 for stroke, 1.13 to 1.74 for cardiovascular mortality and 1.15 to 2.01 for MI. Conclusion Smoking amplified the risk of mortality as well as cardiovascular events and the effect size for CHD appeared to be higher than other events in diabetic patients. Moreover, a trend of decreasing risk was observed among smoking quitters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin ...N6 to improve the problem, cordycepin derivatives (
-
) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound
showed the most obvious inhibitory effect on MCF7 cells with an IC
value of 27.57 ± 0.52 μM, which was much lower than cordycepin. Compound
showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound
promoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound
could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound
induced the apoptosis of MCF7 cells through the mitochondrial pathway.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Humans, throughout the life cycle, from birth to death, are accompanied by the presence of gut microbes. Environmental factors, lifestyle, age and other factors can affect the balance of intestinal ...microbiota and their impact on human health. A large amount of data show that dietary, prebiotics, antibiotics can regulate various diseases through gut microbes. In this review, we focus on the role of gut microbes in the development of metabolic, gastrointestinal, neurological, immune diseases and, cancer. We also discuss the interaction between gut microbes and the host with respect to their beneficial and harmful effects, including their metabolites, microbial enzymes, small molecules and inflammatory molecules. More specifically, we evaluate the potential ability of gut microbes to cure diseases through Fecal Microbial Transplantation (FMT), which is expected to become a new type of clinical strategy for the treatment of various diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The pleiotropic features of obesity, retinal degeneration, polydactyly, kidney abnormalities, cognitive impairment, hypertension, and diabetes found in Bardet-Biedl syndrome (BBS) make this disorder ...an important model disorder for identifying molecular mechanisms involved in common human diseases. To date, 16 BBS genes have been reported, seven of which (BBS1, 2, 4, 5, 7, 8, and 9) code for proteins that form a complex known as the BBSome. The function of the BBSome involves ciliary membrane biogenesis. Three additional BBS genes (BBS6, BBS10, and BBS12) have homology to type II chaperonins and interact with CCT/TRiC proteins and BBS7 to form a complex termed the BBS-chaperonin complex. This complex is required for BBSome assembly. Little is known about the process and the regulation of BBSome formation. We utilized point mutations and null alleles of BBS proteins to disrupt assembly of the BBSome leading to the accumulation of BBSome assembly intermediates. By characterizing BBSome assembly intermediates, we show that the BBS-chaperonin complex plays a role in BBS7 stability. BBS7 interacts with BBS2 and becomes part of a BBS7-BBS2-BBS9 assembly intermediate referred to as the BBSome core complex because it forms the core of the BBSome. BBS1, BBS5, BBS8, and finally BBS4 are added to the BBSome core to form the complete BBSome.
Bardet-Biedl syndrome proteins form a complex known as the BBSome. The details of BBSome assembly are unknown.
The BBSome is assembled via intrinsic protein-protein interactions, some of which involve cytoplasmic chaperonins.
BBSome assembly is a regulated stepwise process.
Understanding the assembly process of the BBSome might help to better understand the molecular mechanisms involved in cilia-related diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tanshinone IIA, a fat-soluble diterpenoid isolated from Salvia miltiorrhiza Bunge, has been shown to attenuate the cerebral ischemic injury. The aim of this study was to examine the effects on ...neuroprotection and microglia activation of Tanshinone IIA. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). We found that Tanshinone IIA significantly reduced infarction volume, alleviated neuronal injuries, reduced the release of TNF-α, IL-1β, and IL-6, increased SOD activity, and decrease the content of MDA in MCAO rats. Hematoxylin and eosin staining, Nissl staining, TUNEL staining and immunofluorescence staining showed that Tanshinone IIA improved the distribution and morphology of neurons in brain tissues and reduced apoptosis. In addition, Co-immunofluorescence staining of rat brain tissues and the mRNA expression levels of CD11b, CD32, iNOS, and Arg-1, CD206, IL-10 in BV2 cells indicated that Tanshinone IIA can downregulate M1 microglia and upregulate M2 microglia in MCAO rats. Further, BV2 microglial cells were subjected to oxygen-glucose deprivation, the protein expression levels were detected by western blot. Tanshinone IIA inhibited the expression levels of NF-κB signaling pathway related proteins. Taken together, this study suggested that Tanshinone IIA modulated microglial M1/M2 polarization
the NF-κB signaling pathway to confer anti-neuroinflammatory effects.
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