Effect of individualized nutritional intervention on head and neck cancer patients receiving radiotherapy.

OBJECTIVE: To explore the effect of individualized nutritional interventions on head and neck cancer (HNC) patients receiving radiotherapy and provide a basis for improving the quality of life for those patients. METHODS: A convenience sampling method was adopted to select HNC patients as the study objects. The Nutritional Risk Screening 2002 scale (NRS2002) was used to screen the nutritional risk in 108 HNC patients receiving radiotherapy, and the patients were randomly divided into control group and observation group. Routine dietary guidance was conducted in the control group, and individualized nutritional intervention was applied in the observation group. RESULTS: Six months after the intervention, the albumin levels (37.40 ± 4.03 g/L), hemoglobin levels (128.70 ± 15.22 g/L), and body mass index scores (BMI) (23.96 ± 3.23 kg/m2) of the observation group were all better than to those of control group (t = 2.370, 2.216, and 3.135, respectively, and P < 0.05 in all). Six months after the intervention, the anxiety and depression scores in observation group (27.6 ± 7.2 points, 27.3 ± 2.2 points) were lower than those in control group (38.6 ± 9.6 points, 37.9 ± 3.3 points). The quality-of-life score in the observation group was higher than that in control group. The nursing satisfaction in the observation group (96.43%) was higher than that in the control group (75.00%). CONCLUSION: The implementation of individualized nutritional intervention has promoted the improvement of laboratory indicators, weight, and BMI of head and neck cancer patients, reduced the risk of malnutrition of head and neck cancer patients, improved their quality of life, reduced the occurrence of adverse reactions during radiotherapy, and promoted long-term efficacy.

Intrathecal drug-infusion system for treating pain in advanced cancer: New research in patient management.

Currently, the treatment of cancer pain in China mainly follows the three-step pain relief principles formulated by the World Health Organization. As research on subarachnoid drug diffusion has intensified, intrathecal drug delivery has been gradually applied in the treatment of diseases, and improved analgesia can be achieved via the continuous infusion of small doses of morphine-derived drugs. This method can not only effectively relieve pain and enhance quality of life but also significantly reduce the incidence of nausea, vomiting, constipation, and other adverse reactions caused by the long-term intensive use of drugs in patients with cancer pain. This study summarizes the development of the intrathecal drug-infusion system for treating cancer pain in patients with advanced cancer and describes the drugs used, the advantages in pain treatment, and key nursing factors before and after device placement to provide a basis for alleviating pain in patients with cancer.

Establishment and evaluation of the impact of a supervisory group for chemotherapy safety management in an oncology department.

BACKGROUND: The nursing model of establishing a chemotherapy safety management supervisory group has guaranteed the safety and effectiveness of intravenous chemotherapy while reducing the adverse effects of chemotherapy and improving patient satisfaction and quality of life. OBJECTIVE: To explore the impact of establishing a nursing supervision group on improving the safety management of patients receiving chemotherapy in the oncology department. METHODS: We selected a total of 60 patients who underwent chemotherapy at the oncology department between January and June 2021 and assigned them to the control group. They received conventional chemotherapy safety management nursing care. We selected another 60 patients undergoing chemotherapy in the oncology department between July and December 2021 and assigned them to the observation group. They received a nursing intervention model facilitated by the chemotherapy safety supervision team. We compared the intervention effects in the two groups. RESULTS: Patient satisfaction was significantly higher in the observation group than in the control group (P< 0.05); the incidence of post-chemotherapy nausea and vomiting was significantly lower in the observation group than in the control group (P< 0.05); and the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients in the observation group were reduced (P< 0.05) and significantly lower than in the control group (P< 0.05). We used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC-QLQ-C30) and found a statistically significant difference in the quality of life of patients before the nursing intervention and on the day of discharge (P< 0.05). CONCLUSION: The establishment of a chemotherapy safety management supervisory group was effective in reducing the incidence of post-chemotherapy nausea and vomiting as well as the patient's psychological burden; it could also improve the quality of life of patients and their satisfaction with nursing care.

Garbractin A, a Polycyclic Polyprenylated Acylphloroglucinol with a 4,11-dioxatricyclo[4.4.2.01,5]Dodecane Skeleton from Garcinia bracteata Fruits.

Garbractin A (1), a structurally complicated polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented 4,11-dioxatricyclo[4.4.2.01,5] dodecane skeleton, was isolated from the fruits of Garcinia bracteata, along with five new biosynthetic analogues named garcibracteatones A-E (2-6). Their structures containing absolute configurations were revealed using spectroscopic data, the residual dipolar coupling-enhanced NMR approach, and quantum chemical calculations. The antihyperglycemic effect of these PPAPs (1-6) was evaluated using insulin-resistant HepG2 cells (IR-HepG2 cells) induced through palmitic acid (PA). Compounds 1, 3, and 4 were found to significantly promote glucose consumption in the IR-HepG2 cells and, therefore, may hold potential as candidates for treating hyperglycemia.

Malnutrition in patients with head and neck cancer undergoing radiotherapy: A cross-sectional study.

OBJECTIVE: In this study, we investigated the prevalence of malnutrition and analyzed the related factors among patients with head and neck cancer (HNC) undergoing radiotherapy. METHODS: We included 108 patients with head and neck cancer undergoing radiotherapy from the oncology and thoracic surgery departments of a comprehensive medical center in Qingdao between January 2019 and June 2020. We used the Nutritional Risk Screening-2002 tool (NRS-2002) to evaluate their nutritional status during radiotherapy. We analyzed the basic sociodemographic information and laboratory indicators of the respondents to examine the impact of these factors on nutritional status. RESULTS: In the 108 patients that we studied, those aged ≥65 years had a significantly higher nutritional risk when compared to patients <65 years of age (P < 0.05). Univariate analysis revealed that a late tumor stage (P = 0.039), the neck being the site of radiotherapy (P = 0.009), the presence of diabetes (P < 0.001), and the presence of anxiety and depression (P = 0.002) were associated with nutritional risks for patients with head and neck cancer undergoing radiotherapy. Multivariate logistic regression analysis identified a late tumor stage, the neck being the radiotherapy site, and combined anxiety and depression as nutritional risk factors in such patients. CONCLUSION: We found a high incidence of malnutrition in patients undergoing radiotherapy for HNC; this highlights the importance of early identification of patients at risk and evaluation of related risk factors to enhance the efficacy of nutritional interventions.

Isolation and antihyperglycemic effects of garcibractinols A-H, intricate polycyclic polyprenylated acylphloroglucinols from the fruits of Garcinia bracteata.

Eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from the fruits of Garcinia bracteata and named garcibractinols A-H. Garcibractinols A-F (compounds 1-6) were bicyclic polyprenylated acylphloroglucinols (BPAPs) sharing a rare bicyclo[4.3.1]decane core. On the other hand, garcibractinols G and H (compounds 7 and 8) shared an unprecedented BPAP skeleton bearing a 9-oxabicyclo[6.2.1]undecane core. The structures andabsolute configurations of compounds 1-8 were determined by spectroscopic analysis,single-crystal X-ray diffraction analysis, and quantum chemical calculation. The breakage of the C-3/C-4 linkage through the retro-Claisen reaction was a key step in the biosynthesis of compounds 7 and 8. The antihyperglycemic effects of the eight compounds were evaluated in insulin-resistant HepG2 cells. At a concentration of 10 µM, compounds 2 and 5-8 significantly increased the glucose consumption in the HepG2 cells. Furthermore, compound 7 was more effective than metformin (which was used as a positive control) in promoting glucose consumption in the cells. The findings of this study suggest that compounds 2 and 5-8 have anti-diabetic effects.

Curcumae rhizoma and its major constituents against hepatobiliary disease: Pharmacotherapeutic properties and potential clinical applications.

BACKGROUND: Hepatobiliary disease currently serves as an urgent health issue in public due to health-modulating factors such as extension of life expectancy, increasingly sedentary lifestyles and over-nutrition. A definite treatment remains lacking owing to different stages of the disease itself and its intricate pathogenesis. Traditional Chinese medicine (TCM) has been gradually popularized in clinic with the satisfactory efficacy and good safety. Curcumae Rhizoma (called E Zhu, EZ in Chinese) is a representative herb, which has been used to treat hepatobiliary disease for thousands of years. PURPOSE: To systematically summarize the recent research advances on the pharmacological activities of EZ and its constituents, explain the underlying mechanisms of preventing and treating hepatobiliary diseases, and assess the shortcomings of existing work. Besides, ethnopharmacology, phytochemicals, and toxicology of EZ have been researched. METHODS: The information about EZ was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG using keywords given below and terms like pharmacological and phytochemical details of this plant. RESULTS: The chemical constituents isolated and identified from EZ, such as terpenoids including ß-elemene, furanodiene, germacrone, etc. and curcuminoids including curcumin, demethoxycurcumin, bisdemethoxycurcumin, etc. prove to have hepatoprotective effect, anti-liver fibrotic effect, anti-fatty liver effect, anti-liver neoplastic effect, and cholagogic effect through TGF-ß1/Smad, JNK1/2-ROS, NF-κB and other anti-inflammatory and antioxidant signaling pathways. Also, EZ is often combined with other Chinese herbs in the treatment of hepatobiliary diseases with good clinical efficacy and no obvious adverse reactions. CONCLUSION: It provides a preclinical basis for the efficacy of EZ as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases. Even so, the further studies still needed to alleviate hepatotoxicity and expand clinical application.

N-trans-Feruloyloctopamine Wakes Up BBC3, DDIT3, CDKN1A, and NOXA Signals to Accelerate HCC Cell Apoptosis.

N-trans-Feruloyloctopamine (FO), a natural compound, was reported in our previous study to inhibit a tumor cell malignant phenotype by AKT- and EMT-related signals and might be used as a promising drug for HCC treatment. However, the specific targets and detailed mechanisms still need to be clarified. Screening with RNA-Seq in Huh7 cells treated with FO revealed that 317 genes were modulated, of which 188 genes were upregulated and 129 genes were downregulated. Real-time cell analyzer and flow cytometry data reveal that tumor cell proliferation and apoptosis were impacted by FO. DAVID bioinformatic data showed that most of the biological process GO terms are related to proliferation and apoptosis. KEGG enrichment analysis showed that FO mainly regulates PI3K-AKT- and apoptosis-related signals, in which BBC3, DDIT3, NOXA, and CDKN1A on the surface serve as the novel targets of FO inducing HCC cell apoptosis. The result implied that FO might exacerbate HCC cell apoptosis by regulating BBC3, DDIT3, CDKN1A, and NOXA signals. The obstacle effect of FO can provide new targets and new credibility for the treatment of liver cancer.

Myxofibrosarcoma of the scalp with difficult preoperative diagnosis: A case report and review of the literature.

BACKGROUND: A myxofibrosarcoma (MFS) is a malignant fibroblastic tumor that tends to occur in the lower and upper extremities. The reported incidence of head and neck MFSs is extremely rare. We report a 46-year-old male with "a neoplasm in the scalp" who was hospitalized and diagnosed with an MFS (highly malignant with massive necrotic lesions) based on histologic and immunohistochemistry evaluations. The magnetic resonance imaging manifestations did not demonstrate the "tail sign" mentioned in several studies, which resulted in a great challenge to establish an imaging diagnosis. The treatment plan is closely associated with the anatomic location and histologic grade, and more importantly, aggressive surgery and adjuvant radiotherapy may be helpful. Hence, we report the case and share some valuable information about the disease. CASE SUMMARY: A 46-year-old male with "a neoplasm in the scalp for 6 mo" was hospitalized. Initially, the tumor was about the size of a soybean, without algesia or ulceration. The patient ignored the growth, did not seek treatment, and thus, did not receive treatment. Recently, the tumor increased to the size of an egg; there was no bleeding or algesia. His family history was unremarkable. No abnormalities were found upon laboratory testing, including routine hematologic, biochemistry, and tumor markers. Computed tomography showed an ovoid mass (6.25 cm × 3.29 cm × 3.09 cm in size) in the left frontal scalp with low density intermingled with equidense strips in adjacent areas of the scalp. Magnetic resonance imaging revealed a lesion with an irregular surface and an approximate size of 3.55 cm × 6.34 cm in the left frontal region, with clear boundaries and visible separation. Adjacent areas of the skull were damaged and the dura mater was involved. Contrast enhancement showed an uneven enhancement pattern. Surgery was performed and postoperative adjuvant radiotherapy was administered to avoid recurrence or metastasis. The post-operative pathologic diagnosis confirmed an MFS. A repeat computed tomography scan showed no local recurrence or distant metastasis 19 mo post-operatively. CONCLUSION: The case reported herein of MFS was demonstrated in an extremely rare location on the scalp and had atypical magnetic resonance imaging findings, which serves as a reminder to radiologists of the possibility of this diagnosis to assist in clinical treatment. Given the special anatomic location and the high malignant potential of this rare tumor, combined surgical and adjuvant radiotherapy should be considered to avoid local recurrence and distant metastasis. The significance of regular follow-up is strongly recommended to improve the long-term survival rate.

The Synergistic Antitumor Effect of Tanshinone IIA Plus Adriamycin on Human Hepatocellular Carcinoma Xenograft in BALB/C Nude Mice and Their Influences on Cytochrome P450 CYP3A4 In Vivo.

OBJECTIVE: Hepatocellular carcinoma is one of the most common diseases that seriously threaten human life and health. In this study, we evaluated the inhibitory effect of tanshinone IIA (Tan IIA) combined with adriamycin (ADM) on human hepatocellular carcinoma and developed a platform to assess the function if Chinese herbal ingredients combined with chemotherapy drugs have synergistic antitumor effects in vivo. METHODS: Established animal model of human hepatocarcinoma HepG2 cell in nude mice. Mice were divided into model control group, Tan IIA group, ADM group, and Tan IIA + ADM group. The changes from general condition, weight, tumor volume, and inhibition rate were observed. The data were gathered from serum AST level and histopathological changes. The content and activity of cytochrome P450 were determined by spectrophotometric analysis. CYP3A4 protein expression was analyzed by western blotting. The binding model crystal structure of Tan IIA and ADM with pregnane X receptor (PXR) was evaluated by Discovery Studio 2.1. RESULTS: A combination of Tan IIA with ADM could improve life quality by relieving ADM toxicity, decreasing tumor volume, declining serum AST level, and improving liner pathological section in tumor-bearing mice. The inhibitory rates of Tan IIA, ADM, and cotreatment were 32.77%, 60.96%, and 73.18%, respectively. The Tan IIA group significantly enhanced the content of cytochrome b5, P450, and erythromycin-N-demethylase activity. CYP3A4 protein expression was enhanced obviously by the Tan IIA + ADM group. Virtual molecular docking showed that both Tan IIA and ADM could be stably docked with the same binding site of PXR but different interactions. CONCLUSIONS: Tan IIA in combination with ADM could improve the life quality in tumor-bearing mice and enhance the antitumor effect. The Tan IIA group increased the concentration of cytochrome P450 enzymes and activity. Combined Tan IIA with ADM could upregulate the CYP3A4 protein expression and make relevant interaction with protein PXR by virtual docking.

Pepsin promotes IL-8 signaling-induced epithelial-mesenchymal transition in laryngeal carcinoma.

BACKGROUND: Laryngopharyngeal reflux (LPR), with its increasing morbidity, is attracting considerable attention. In recent years, the causal role between LPR and laryngeal carcinoma has been debated. The main harmful component of LPR is pepsin, which has been shown to induce mucosal inflammation by damaging the mucous membrane. Thus, pepsin is linked to an increased risk of laryngeal carcinoma, although the potential mechanism remains largely unknown. METHODS: The human laryngeal carcinoma cell lines Hep-2 and Tu212 were exposed to different pepsin concentrations and the morphology, proliferation, migration, secretion of inflammatory cytokines, and epithelial-mesenchymal transition (EMT) of the cells were assessed. To evaluate whether interleukin-8 (IL-8) had a causal relationship with pepsin and EMT, an IL-8 inhibitor was used to suppress IL-8 secretion during pepsin exposure and the expression of EMT markers, cell proliferation, and migration were analyzed. RESULTS: Pepsin promoted proliferation, colony formation, migration, and IL-8 secretion of Hep-2 and Tu212 cells in vitro. Furthermore, increased pepsin concentrations changed the morphology of Hep-2 and Tu212 cells; levels of the epithelial marker E-cadherin were reduced and those of mesenchymal markers vimentin and ß-catenin and the transcription factors snail and slug were elevated. A similar effect was observed in laryngeal carcinoma tissues using immunohistochemistry. IL-8 level was reduced and EMT was restored when pepsin was inhibited by pepstatin. EMT was weakened after exposure to the IL-8 inhibitor, with significant reduction in pepsin-induced cell proliferation and migration. CONCLUSIONS: Pepsin may induce EMT in laryngeal carcinoma through the IL-8 signaling pathway, which indicates that it has potential role in enhancing cell proliferation and metastasis of laryngeal carcinoma.

Optimized Generation of Primary Human Epithelial Cells from Larynx and Hypopharynx: A Site-Specific Epithelial Model for Reflux Research.

Laryngopharyngeal reflux (LPR) induces a differential damage effect on several anatomic sites within the larynx and hypopharynx; therefore, an in vitro model is needed for each anatomic site. This study aimed to establish a primary culture method for human laryngeal and hypopharyngeal epithelial cells derived from multiple anatomic sites. Surgical mucosa specimens were treated with a two-step enzymatic strategy to establish a primary culture. Of the 46 samples, primary cultivation was achieved successfully with 36 samples, and the positive ratio was 78.3%. In addition, flow cytometry revealed that these primary cells were epithelial cells with a purity of 94.9%. The proliferative ability was confirmed by positive staining for Ki-67. Laryngeal and hypopharyngeal epithelial cells from multiple sites exhibited similar epithelial morphology and positive cytokeratin expression. These cells can be cultured to passage 4. In summary, we successfully established the in vitro epithelial model of larynx and hypopharynx subsites, which may potentially be used as a platform for reflux research, especially for site-specific damage effect.

Preparation of 4-Flexible Amino-2-Arylethenyl-Quinoline Derivatives as Multi-target Agents for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder of aged people. The development of multitarget-directed ligands (MTDLs) to act as multifunctional agents to treat this disease is the mainstream of current research. As a continuation of our previous studies, a series of 4-flexible amino-2-arylethenylquinoline derivatives as multi-target agents was efficiently synthesized and evaluated for the treatment of AD. Among these synthesized derivatives, some compounds exhibited strong self-induced Aß1⁻42 aggregation inhibition and antioxidant activity. The structure-activity relationship was summarized, which confirmed that the introduction of a flexible amino group featuring a N,N-dimethylaminoalkylamino moiety at the 4-position increased the Aß1⁻42 aggregation inhibition activity, with an inhibition ratio of 95.3% at 20 µM concentration. Compound 6b1, the optimal compound, was able to selectively chelate copper (II), and inhibit Cu2+-induced Aß aggregation effectively. It also could disassemble the self-induced Aß1⁻42 aggregation fibrils with a ratio of 64.3% at 20 µM concentration. Moreover, compound 6b1 showed low toxicity and a good neuroprotective effect against Aß1⁻42-induced toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated compound 6b1 significantly reversed scopolamine-induced memory deficit in mice. Taken together, these results suggested that compound 6b1 was a promising multi-target compound worthy of further study for AD.

Matrine combined with cisplatin synergistically inhibited urothelial bladder cancer cells via down-regulating VEGF/PI3K/Akt signaling pathway.

BACKGROUND: Cisplatin is one of the first-line drugs for urothelial bladder cancer (UBC) treatment. However, its considerable side effects and the emergence of drug resistance are becoming major limitations for its application. This study aimed to investigate whether matrine and cisplatin could present a synergistic anti-tumor effect on UBC cells. METHODS: Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of the UBC cells. Wound healing assay and transwell assay were applied respectively to determine the migration and invasion ability of the cells. The distribution of cell cycles, the generation of reactive oxygen species (ROS) and the apoptosis rate were detected by flow cytometry (FCM). The expressions of the relative proteins in apoptotic signal pathways and the epithelial-mesenchymal transition (EMT) related genes were surveyed by western blotting. The binding modes of the drugs within the proteins were detected by CDOCKER module in DS 2.5. RESULTS: Both matrine and cisplatin could inhibit the growth of the UBC cells in a time- and dose-dependent manner. When matrine combined with cisplatin at the ratio of 2000:1, they presented a synergistic inhibitory effect on the UBC cells. The combinative treatment could impair cell migration and invasion ability, arrest cell cycle in the G1 and S phases, increase the level of ROS, and induce apoptosis in EJ and T24 cells in a synergistic way. In all the treated groups, the expressions of E-cadherin, ß-catenin, Bax, and Cleaved Caspase-3 were up-regulated, while the expressions of Fibronectin, Vimentin, Bcl-2, Caspase-3, p-Akt, p-PI3K, VEGFR2, and VEGF proteins were down-regulated, and among them, the combination of matrine and cisplatin showed the most significant difference. Molecular docking algorithms predicted that matrine and cisplatin could be docked into the same active sites and interact with different residues within the tested proteins. CONCLUSIONS: Our results suggested that the combination of matrine and cisplatin could synergistically inhibit the UBC cells' proliferation through down-regulating VEGF/PI3K/Akt signaling pathway, indicating that matrine may serve as a new option in the combinative therapy in the treatment of UBC.

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way.

BACKGROUND: The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers. METHODS: Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins. RESULTS: Both tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin. CONCLUSIONS: Tanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.

Methotrexate intercalated layered double hydroxides with different particle sizes: structural study and controlled release properties.

To study the influence of particle size on release properties, drug efficacy and other properties, a series of methotrexate intercalated layered double hydroxides (MTX/LDHs) nanohybrids with different particle sizes were synthesized through traditional coprecipitation method, by using the mixture of water and polyethylene glycol (volume ratio is 3:1) as solvent. The relationship between particle size and hydrothermal treatment conditions (i.e., time and temperature) had been systematically investigated, and the results indicate that the particle size can be precisely controlled between 70 and 300 nm. Elemental C/H/N and inductive coupled plasma (ICP) analysis indicated that different hydrothermal treatment almost has no effect on compositions of the nanohybrids. X-ray diffraction (XRD) patterns and fourier transform infrared spectroscopy (FTIR) investigations manifested the successful intercalation of MTX anions. MTX/LDHs particles exhibited hexagonal platelet morphology with round corner, due to the adsorption of MTX anions on positively charged LDHs surface. In addition, the crystallinity of MTX/LDHs increased with the particle diameters and the thermal stability of MTX anions was enhanced by holding together with LDHs layers. The in vitro release showed that bigger particles have much longer release duration, and the bioassay tests indicated that bigger particles are more efficient in the suppression of the tumor cells.

Scutellaria extract decreases the proportion of side population cells in a myeloma cell line by down-regulating the expression of ABCG2 protein.

BACKGROUND AND AIMS: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. MATERIALS AND METHODS: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. RESULTS: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of 1-75µg/mL. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. CONCLUSIONS: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.

Therapeutic effects of melatonin on heatstroke-induced multiple organ dysfunction syndrome in rats.

Melatonin reportedly exerts beneficial effects to attenuate multiple organ dysfunction syndrome (MODS) in septic shock. Heatstroke resembles septic shock in many aspects. Thus, this study was performed on the anesthetized rats by using heat exposure to induce heatstroke-associated MODS. We evaluated the effect of melatonin, a versatile molecule synthesized in the pineal gland and in many organs, in heatstroke rats and showed that melatonin (0.2-5.0 mg/kg of body weight, i.v., immediately after the start of heat stress) significantly (i) attenuated hyperthermia, hypotension and hypothalamic ischemia and hypoxia, (ii) reduced plasma index of the toxic oxidizing radicals like nitric oxide metabolites and hydroxyl radicals, (iii) diminished plasma index of hepatic and renal dysfunction like creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase, (iv) attenuated plasma systemic inflammation response molecules like soluble intercellular and lesion molecule-1, E-selectin, tumor necrosis factor-alpha, interleukin (IL)-1ß, and IL-6, (v) promoted plasma levels of an anti-inflammatory cytokine IL-10, (vi) reduced an index of infiltration of polymorphonuclear neutrophils in the lung like myeloperoxidase activity, and (vii) promoted the survival time to fourfold compared with the heatstroke alone group. Thus, melatonin could be a novel agent for the treatment of heatstroke animals or patients in the early stage.

[Immunohistochemical study of tumor necrosis factor-alpha expression in the lungs and small intestines in hyperthermia-LPS co-stressed rats].

OBJECTIVE: To investigate the effects of co-exposure to hyperthermia and lipopolysaccharides (LPS) on tumor necrosis factor-alpha (TNF-alpha) expression in the lungs and small intestines of rats. METHODS: Male pathogen-free Wistar rats were randomly assigned into saline-injected normothermic control (C), saline heat exposure (H), LPS normothermic control (L), and LPS plus heat exposure (HL) groups. The rats in H and HL groups were exposed in a chamber at an ambient dry bulb temperature (Tdb) of 35.0-/+0.5 degrees celsius;, and those in C and L groups to 26-/+0.5 degrees celsius;. In L and HL groups, the rats were given an intravenous injection of LPS 10 mg/kg via the tail vein to induce endotoxemia, and those in C and H group received 10 ml/kg injection. The plasma levels of sTNFrI and sTNFrII were detected at different time points using ELISA. The expression of TNF-alpha in the lungs and small intestines was detected by immunohistochemical SABC method, and the damage of the lungs and small intestines evaluated histologically 120 min after the treatment. RESULTS: Co-exposure to hyperthermia and LPS caused significantly enhanced expressions of TNF-alpha and its receptor sTNFrI and sTNFrII in the plasma and tissues and obvious histopathological damage in the lung and small intestines. CONCLUSION: Co-stress of hyperthermia and LPS-induced toxicity is associated with the expression of TNF-alpha in the lung and small intestines.