• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.224-230
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• 2024

Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known. Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVA-induced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-β signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4013-4018
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• 2015

Objective: To explore the clinical application of recombinant human endostatin (Endostar) in the treatment of patients with non-small cell lung cancer (NSCLC) in Chinese mainland. Materials and Methods: A total of 75 patients diagnosed as NSCLC were randomly divided into control group (37 cases) and treatment group (38 cases). Control group was treated with postoperative complementary chemotherapy containing two-agent platinum protocol on postoperative d21, 3 weeks as a cycle, for totally 4~6 cycles. On this basis, treatment group was added with Endostar $7.5mg/m^2$ on postoperative d8~9, 3~4 h/time, qd, 14 weeks as a cycle, for totally 4 cycles. The interval between every two cycles was 7 d. The 5-year progression-free survival (PFS), 5-year survival time and complications in both groups were observed. Results: Compared with control group, the average PFS increased evidently in treatment group by 9.8 months (41.6 months vs. 31.8 months), and there was significant difference (P<0.05). And the median PFS was 42.5 months in treatment group, obviously longer than that in control group (33.7 months) by 8.8 months (P<0.05). Additionally, the 5-year overall survival rate (OS), average survival time and median survival time (MST) were 47.4%, 50.1 months and 59.3 months in treatment group, significantly higher than the 29.7%, 42.1 months and 43.5 months in control group (P<0.05). Only 1 patient showed poor healing of surgical wound in treatment group, but no surgery-associated complication was found in control group. Moreover, the postoperative complementary therapy-connected complication rates were 63.2% (24/38) and 59.5% (22/37) in treatment group and control group respectively, but there was no significant difference (P>0.05). Conclusions: The application of Endostar combined with sensitive platinum-contained chemotherapeutic agents in the postoperative complementary chemotherapy can be widely used in clinic because it can significantly prolong the long-term survival time of patients with NSCLC.

• Journal of Korean Neurosurgical Society
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• v.63 no.6
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• pp.698-706
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• 2020

Objective : To study the physiochemical characteristics of podophyllotoxin (PPT) conjugated stearic acid grafted chitosan oligosaccharide micelle (PPT-CSO-SA), and evaluate the ability of the potential antineoplastic effects against glioma cells. Methods : PPT-CSO-SA was prepared by a dialysis method. The quality of PPT-CSO-SA including micellar size, zeta potential, drug encapsulation efficiency and drug release profiles was evaluated. Glioma cells were cultured and treated with PPT and PPT-CSO-SA. The ability of glioma cells to uptake PPT-CSO-SA was observed. The proliferation of glioma cells was determined by 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The apoptosis and morphology of U251 cells were observed by 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) dye staining. Cell cycle analysis was performed by flow cytometry. The migration ability of U251 cells was determined by wound healing test. Results : PPT-CSO-SA had nano-level particle size and sustained release property. The encapsulation efficiency of drug reached a high level. The cellular uptake percentage of PPT in glioma cells was lower than that of PPT-CSO-SA (p<0.05). The inhibitory effect of PPT-CSO-SA on glioma cells proliferation was significantly stronger than that of PPT (p<0.05). The morphologic change of apoptosis cell such as shrinkage, karyorrhexis and karyopyknosis were observed. The percentage of U251 cells in G2/M phase increased significantly in the PPT-CSO-SA group compared with PPT group (p<0.05). Compared with the PPT group, the cell migration ability of the PPT-CSO-SA group was significantly inhibited after 12 and 24 hours (p<0.05). Conclusion : PPT-CSO-SA can effectively enhance the glioma cellular uptake of drugs, inhibit glioma cells proliferation and migration, induce G2/M phase arrest of them, and promote their apoptosis. It may be a promising anti-glioma nano-drug.

• Archives of Plastic Surgery
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• v.47 no.3
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• pp.217-222
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• 2020

Background Surgical reconstruction of chronic wounds is often infeasible due to infection, comorbidities, or poor viability of local tissues. The aim of this study was to describe the authors' technique for improving the regenerative and antimicrobial potential of a combination of modified nanofat and platelet-rich plasma (PRP) in nonhealing infected wounds. Methods Fourteen patients met the inclusion criteria. Fat tissue was harvested from the lower abdomen following infiltration of a solution of 1,000 mL of NaCl solution, 225 mg of ropivacaine, and 1 mg of epinephrine. Aspiration was performed using a 3-mm cannula with 1-mm holes. The obtained solution was decanted and mechanically emulsified, but was not filtered. Non-activated leukocyte-rich PRP (naLR-PRP) was added to the solution before injection. Patients underwent three sessions of injection of 8-mL naLR-PRP performed at 2-week intervals. Results Thirteen of 14 patients completed the follow-up. Complete healing was achieved in seven patients (53.8%). Four patients (30.8%) showed improvement, with a mean ulcer width reduction of 57.5%±13.8%. Clinical improvements in perilesional skin quality were reported in all patients, with reduced erythema, increased thickness, and increased pliability. An overall wound depth reduction of 76.6%±40.8% was found. Pain was fully alleviated in all patients who underwent re-epithelization. A mean pain reduction of 42%±33.3% (as indicated by visual analog scale score) was found in non-re-epithelized patients at a 3-month follow-up. Conclusions The discussed technique facilitated improvement of both the regenerative and the antimicrobial potential of fat grafting. It proved effective in surgically-untreatable infected chronic wounds unresponsive to conventional therapies.

• Journal of Life Science
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• v.34 no.5
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• pp.287-295
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• 2024

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, necessitating novel therapeutic strategies. The chemotherapeutic agents used to treat HCC patients are toxic and have serious side effects. Therefore, we investigated the efficacy of anticancer drugs that reduce side effects by targeting tumor cells without causing cytotoxicity in healthy hepatocytes. Berberine, an isoquinoline alkaloid derived from plant compounds, has emerged as a potential candidate for cancer treatment due to its diverse pharmacological properties. The effect of berberine on HepG2 cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. HepG2 cell proliferation was determined through a colony-forming assay. The effects of berberine on HepG2 cell migration were evaluated using a wound-healing assay. Berberine inhibited the proliferation of HepG2 cells, as well as colony formation and migration. Berberine treatment increased the expression of autophagy-related genes and proteins, including Beclin-1 and LC3-II, and elevated the activities and mRNA expression of Caspase-9 and Caspase-3. Additionally, in experiments utilizing the Cell-Derived Xenograft animal model, berberine treatment reduced tumor size and weight in a concentration-dependent manner. These results demonstrate the potential of berberine as a versatile anticancer agent with efficacy in both cellular and animal models of hepatocellular carcinoma. The findings herein shed light on berberine's efficacy against HCC, presenting opportunities for targeted and personalized therapeutic interventions.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.368-378
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• 2024

Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44^highCD133^high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

• Journal of Life Science
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• v.25 no.10
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• pp.1156-1163
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• 2015

The present study investigated the immunomodulatory properties of four different medicinal plants in a cyclophosphamide-treated Balb/c mouse model. One of the four plants, Ulmus macrocarpa, showed partial resistance against immune suppression induced by cyclophosphamide. The bark of U. macrocarpa, commonly known as the Chinese elm, has been used as a pharmaceutical material in Korean traditional medicine to treat bacterial inflammation and induce wound healing. In this study, water extract of U. macrocarpa, named DEU-7, was used for its immunomodulating functional activity. DEU-7 increased the weight of the spleen and the number of splenocytes but did not significantly affect the liver, kidney, and thymus in vivo. A splenocyte viability assay confirmed that DEU-7 influenced ex vivo splenocyte survival. DEU-7 also increased the levels of cytokines, such as IL-2 and IL-4, and immunoglobulins, such as IgM, IgG, and IgA. These results indicated that DEU-7 is involved in the activation of T and B lymphocytes. In addition, DEU-7 was able to maintain the production of cytokines, such as TNF-α, IL-12, and IFN-γ, in the condition of cyclophosphamide-induced immune suppression, suggesting that DEU-7 activated innate immune cells, even under immune suppression. We concluded that DEU-7 aids immunological homeostasis, thereby preventing immune suppression, and aids both innate and adaptive immune response by maintaining the levels of various cytokines and immunoglobulins. Consequently, it is worth investigating the potential of DEU-7 as a supplemental source for immune-enhancing agents.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.867-882
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• 1997

Safflower(Carthamus tinctorius $Linn\acute{e}$ has been traditionally used for the treatment of blood stasis, and Dipsasi Radix has been used as a drug for fracture in Chinese medicine. The purpose of present study was to examine the biologic effects of safflower extract and Disasi radix extracts on the periodontal. ligament cells and osteoblastic cells and on the wound healing of rat calvarial defect. The ethanolic extract of safflower blossom, safflower seed and Dipsasi Radix(125, 250, and 500 ${\mu}g/ml$) were prepared as test group, and PDGF-BB(lOng/ml) and unsafonifiable fraction of Zea Mays L.(125, 250, and 500 ${\mu}g/ml$) were employed as positive control. The effects of each agents on the growth and survival, ALPase activity, expression of PDGF-BB receptor, chemotactic response of PDL cell and ATCC human osteosarcoma MG63 cells in vitro were examined. The tissue regenerative effect of each extracts was evaluated by histomorphometric measuring of newly formed bone on the 8mm defect in rat calvaria after oral administration of 3 different dosages groups : 0.02, 0.1 and 0.35g/kg, per day. It was also employed the same dosages of unsaponifiable fraction of Zea Mays L. as positive controls. Safflower blossom extract, safflower seed extract, and Dipsasi Radix extract stimulate the cellular activity of MG63 cells in concentration range of $125-500{\mu}g/ml$, and safflower bolssom extract and safflower seed extract stimulate also the cellular activity of periodontal ligament cells in concentration range of $250-500{\mu}g/ml$. In activity of ALPase, $250-500{\mu}g/ml$ of safflower blossom extracts showed significant stimulating effects on MG63 cells, and the same concentration range of safflower seed extracts showed significant effect on periodontal ligament cells. In the recovery on PDGF-BB receptor expression which was depressed by $IL-1{\beta}$, $125-250{\mu}g/ml$ of safflower blossom extracts and $250-500{\mu}g/ml$ of safflower seed extracts showed significant increasing effect on MG63 cells, and $500{\mu}g/ml$ of safflower blossom extract and $250-500{\mu}g/ml$ of safflower seed extracts showed significant effect on periodontal ligament cells. In chemotactic response, among all tested group, safflower seed extracts only were chemotactic to MG63 cells and periodontal ligament cells in concentration range of $125-500{\mu}g/ml$. Also in the view of bone regeneration in rat calvarial defect model, the only group that was orally administrated 0.35g/kg, day of safflower seed extract showed significant new bone formation. These results suggested that safflower extracts might have a potential possibilities as an useful drug for adjunct to treatment for regeneration of periodontal defect.