Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer.

Advanced colorectal cancer (CRC) responds poorly to current adjuvant therapies, partially due to its immunosuppressive intestinal microenvironment. We found that myeloid-derived suppressor cells (MDSCs) were enriched in orthotopic tumors due to treatment-induced succinate release, which activated tuft cells and upregulated interleukin 25 (IL-25) and interleukin 13 (IL-13). We engineered a cabozantinib (Cabo)-encapsulated and maytansine (DM1)-conjugated synthetic high-density lipoprotein (ECCD-sHDL) to modulate the tumor microenvironment. DM1 induced immunogenic cell death and promoted the maturation of dendritic cells. Meanwhile, Cabo alleviated DM1-induced succinate release, preventing tuft cell activation, downregulating IL-25 and IL-13 secretion, and reducing intratumoral MDSC infiltration. ECCD-sHDL increased the densities of active cytotoxic T lymphocytes (CTLs) and M1 macrophages in the tumors, effectively inhibiting tumor growth and metastasis, thereby prolonging survival in murine CRC models. Our study sheds light on the mechanism of treatment-induced immunosuppression in orthotopic CRC and demonstrates that this combinatorial therapy could be an effective treatment for CRC.

TAF15 inhibits p53 nucleus translocation and promotes HCC cell 5-FU resistance via post-transcriptional regulation of UBE2N.

Chemotherapy resistance is an important factor responsible for the low 5-year survival rate of hepatocellular carcinoma (HCC) patients. Ubiquitin-conjugating enzyme E2N (UBE2N) is a cancer-associated ubiquitin-conjugating enzyme that is expressed in HCC tissues, and its high expression is associated with a poor prognosis. This study explored the role played by UBE2N in development of 5-fluorouracil (5-FU) resistance in HCC cells. Three HCC cell lines (HepG2 [p53 wild type], Huh7 [p53 point mutant type], Hep3B [p53 non-expression type]), and one normal liver cell line (MIHA) were used in our present study. The IC50 value of 5-FU was determined using a cell counting kit-8 (CCK-8) assay. Cell viability was assessed by colony formation assays. TUNEL assays and flow cytometry were used to analyze cell apoptosis. RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to confirm the binding relationship between UBE2N mRNA and TAF15 protein. Our results showed that TAF15 and UBE2N were highly expressed in HCC cells. UBE2N inhibited the translocation of p53 protein into the cell nucleus to increase 5-FU resistance, as reflected by an increased IC50 value, an increase in cell viability, and a reduction in cell apoptosis. Overexpression of p53 reduced 5-FU resistance, but that effect could be reversed by UBE2N overexpression. TAF15 protein bound to and stabilized UBE2N mRNA, thereby inhibiting p53 translocation into the nucleus and promoting 5-FU resistance in HCC cells. Collectively, our present study identified a novel mechanism by which TAF15/UBE2N regulates p53 distribution to increase 5-FU resistance. Our results also suggest potential therapeutic strategies for treating HCC.

METTL3-driven m6A modification of lncRNA FAM230B suppresses ferroptosis by modulating miR-27a-5p/BTF3 axis in gastric cancer.

Our previous research revealed the apoptosis-inhibiting effect of lncRNA FAM230B in gastric cancer (GC). While its role on ferroptosis of GC remain unexplored. In this study, the m6A level and RNA stability regulation of METTL3 on FAM230B was detected by m6A quantification, stability assays, MeRIP, and their interaction was confirmed by RIP, and RNA pull-down assays. The level of ferroptosis was detected by flow cytometry, MDA and GSH level assessments, and electron microscopy. Gene expression was detected by quantitative real-time PCR, western blot, and immunofluorescence. The miR-27a-5p and BTF3 interaction was predicted with TargetScan and confirmed by dual-luciferase assay. Here, elevated levels of METTL3 and FAM230B were observed in GC tissues and cell lines. METTL3 was confirmed to bind with FAM230B RNA. Furthermore, silencing METTL3 reduced FAM230B m6A levels and stability, leading to decreased FAM230B and increased miR-27a-5p expressions. FAM230B knockdown favored ferroptosis and increased BTF3 expression, while its overexpression mitigated erastin-induced ferroptosis in GC cells. Additionally, BTF3 overexpression was found to negate miR-27a-5p's ferroptosis-promoting effects in GC cells. Collectively, our study demonstrates that the m6A modification of FAM230B by METTL3 plays a crucial role in promoting GC progression by reducing ferroptosis, through the modulation of the miR-27a-5p/BTF3 axis.

Ozone Therapy for Breast Cancer: An Integrative Literature Review.

Breast cancer is the most prevalent form of cancer in women. Despite significant advances in conventional treatment, additional safer complementary treatment options are needed. Recently, ozone therapy has been considered as a type of medical adjunctive treatment that could inhibit cancer cell survival and reduce chemoresistance. However, only a few studies have been conducted on its use in breast cancer, and the optimal dosage and time of administration are unknown. Currently, preclinical studies suggest that ozone alone or in combination with chemotherapy is an effective method for inhibiting breast cancer cell growth. However, rather than investigating the effects of ozone as an antitumor therapy, current clinical trials have generally assessed its effect as an adjunctive therapy for reducing chemotherapy-induced side effects, increasing oxygen tension, normalizing blood flow, restoring blood lymphocytes more rapidly, and reducing fatigue symptoms. In this article, the use of ozone as a medical adjunctive treatment for breast cancer and its role in integrative therapy are summarized and discussed.

Association between glycolysis markers and prognosis of liver cancer: a systematic review and meta-analysis.

BACKGROUND: In recent years, the capacity of tumor cells to maintain high levels of glycolysis, even in the presence of oxygen, has emerged as one of the main metabolic traits and garnered considerable attention. The purpose of this meta-analysis is to investigate the prognostic value of glycolysis markers in liver cancer. METHODS: PubMed, Embase, and Cochrane Library databases were searched for articles on glycolytic marker expression levels associated with the prognosis of liver cancer until April 2023. Stata SE14.0 was used to calculate the aggregate hazard ratios and 95% confidence intervals. RESULTS: Thirty-five studies were included. The worse overall survival (OS) (P < 0.001), disease-free survival (DFS) (P = 0.001), recurrence-free survival (RFS) (P = 0.004), and time to recurrence (TTR) (P < 0.001) were significantly associated with elevated expression of glycolysis markers. Higher expression of PKM2 (P < 0.001), STMN1 (P = 0.002), MCT4 (P < 0.001), GLUT1 (P = 0.025), HK-2 (P < 0.001), and CA9 (P < 0.001) were significantly related to shorter OS. Increased levels of PKM2 (P < 0.001), CA9 (P = 0.005), and MCT4 (P < 0.001) were associated with worse DFS. Elevated PKM2 expression (P = 0.002) was also associated with poorer RFS in hepatocellular carcinoma patients. GLUT2 expression was not correlated with the prognosis of liver cancer (P = 0.134). CONCLUSIONS: Elevated expression of glycolysis markers was associated with worse OS, DFS, RFS, and TTR in patients with liver cancer. Therefore, these glycolysis markers could serve as potential prognostic markers and therapeutic targets in liver cancer. TRIAL REGISTRATION: PROSPERO registration: CRD42023469645.

Morphological and metabolic asymmetries of the thalamic subregions in temporal lobe epilepsy predict cognitive functions.

Both morphological and metabolic imaging were used to determine how asymmetrical changes of thalamic subregions are involved in cognition in temporal lobe epilepsy (TLE). We retrospectively recruited 24 left-TLE and 15 right-TLE patients. Six thalamic subnuclei were segmented by magnetic resonance imaging, and then co-registered onto Positron emission tomography images. We calculated the asymmetrical indexes of the volumes and normalized standard uptake value ratio (SUVR) of the entire and individual thalamic subnuclei. The SUVR of ipsilateral subnuclei were extensively and prominently decreased compared with the volume loss. The posterior and medial subnuclei had persistently lower SUVR in both TLE cases. Processing speed is the cognitive function most related to the metabolic asymmetry. It negatively correlated with the metabolic asymmetrical indexes of subregions in left-TLE, while positively correlated with the subnuclei volume asymmetrical indexes in right-TLE. Epilepsy duration negatively correlated with the volume asymmetry of most thalamic subregions in left-TLE and the SUVR asymmetry of ventral and intralaminar subnuclei in right-TLE. Preserved metabolic activity of contralateral thalamic subregions is the key to maintain the processing speed in both TLEs. R-TLE had relatively preserved volume of the ipsilateral thalamic volume, while L-TLE had relatively decline of volume and metabolism in posterior subnucleus.

MicroRNA-194-3p impacts autophagy and represses rotavirus replication via targeting silent information regulator 1.

BACKGROUND: Rotavirus (RV) is the main cause of serious diarrhea in infants and young children worldwide. Numerous studies have demonstrated that RV use host cell mechanisms to motivate their own stabilization and multiplication by degrading, enhancing, or hijacking microRNAs (miRNAs). Therefore, exploring the molecular mechanisms by which miRNAs motivate or restrain RV replication by controlling different biological processes, including autophagy, will help to better understand the pathogenesis of RV development. This study mainly explored the effect of miR-194-3p on autophagy after RV infection and its underlying mechanism of the regulation of RV replication. METHODS: Caco-2 cells were infected with RV and used to measure the expression levels of miR-194-3p and silent information regulator 1 (SIRT1). After transfection with plasmids and RV infection, viral structural proteins, RV titer, cell viability, and autophagy-linked proteins were tested. The degree of acetylation of p53 was further investigated. A RV-infected neonatal mouse model was constructed in vivo and was evaluated for diarrhea symptoms and lipid droplet formation. RESULTS: The results showed that miR-194-3p was reduced but SIRT1 was elevated after RV infection. Elevation of miR-194-3p or repression of SIRT1 inhibited RV replication through the regulation of autophagy. The overexpression of SIRT1 reversed the effects of miR-194-3p on RV replication. The upregulation of miR-194-3p or the downregulation of SIRT1 repressed RV replication in vivo. MiR-194-3p targeted SIRT1 to decrease p53 acetylation. CONCLUSION: These results were used to determine the mechanism of miR-194-3p in RV replication, and identified a novel therapeutic small RNA molecule that can be used against RV.

Deoxyshikonin inhibited rotavirus replication by regulating autophagy and oxidative stress through SIRT1/FoxO1/Rab7 axis.

BACKGROUND: Rotavirus (RV) is a double-stranded RNA virus. RV prevention and treatment remain a major public health problem due to the lack of clinically specific drugs. Deoxyshikonin is a natural compound isolated from the root of Lithospermum erythrorhizon and one of the shikonin derivatives which owns remarkable therapeutic effects on multiple diseases. The purpose of this research was to inquire Deoxyshikonin's role and mechanism in RV infection. METHODS: Deoxyshikonin's function in RV was estimated using Cell Counting Kit-8 analysis, cytopathic effect inhibition assay, virus titer determination, quantitative real-time PCR, enzyme linked-immunosorbent assay, Western blot, immunofluorescence, and glutathione levels detection. Also, Deoxyshikonin's mechanism in RV was appraised with Western blot, virus titer determination, and glutathione levels detection. Moreover, Deoxyshikonin's function in RV in vivo was determined using animal models, and diarrhea score analysis. RESULTS: Deoxyshikonin owned anti-RV activity and repressed RV replication in Caco-2 cells. Furthermore, Deoxyshikonin reduced autophagy and oxidative stress caused by RV. Mechanistically, Deoxyshikonin induced low protein levels of SIRT1, ac-Foxo1, Rab7, VP6, low levels of RV titers, low autophagy and oxidative stress. SIRT1 overexpression abolished the effects of Deoxyshikonin on RV-treated Caco-2 cells. Meanwhile, in vivo research affirmed that Deoxyshikonin also possessed anti-RV function, and this was reflected in increased survival rate, body weight, GSH levels, and decreased diarrhea score, RV virus antigen, LC-3II/LC3-I. CONCLUSION: Deoxyshikonin reduced RV replication through mediating autophagy and oxidative stress via SIRT1/FoxO1/Rab7 pathway.

Biscroyunoid A, an Anti-Hepatic Fibrotic 19-nor-Clerodane Diterpenoid Dimer with a C-16-C-12' Linkage from Croton yunnanensis.

Biscroyunoid A (1), a 19-nor-clerodane diterpenoid dimer featuring a unique C-16-C-12' linkage and containing an unusual 4,7-dihydro-5H-spiro[benzofuran-6,1'-cyclohexane] motif, together with its biosynthetic precursor, croyunoid A (2), were isolated from Croton yunnanensis. Their structures were determined by spectroscopic, computational, and single-crystal X-ray diffraction methods. Compound 1 exerted an antihepatic fibrosis effect in LX-2 cells via inhibition of TGFß-Smad2/3 signaling.

Glochodpurnoid B from Glochidion puberum Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Colorectal Cancer Cells.

Glochidpurnoids A and B (1 and 2), two new coumaroyl or feruloyl oleananes, along with 17 known triterpenoids (3-19) were obtained from the stems and twigs of Glochidion puberum. Their structures were elucidated by extensive spectroscopic data analyses, chemical methods, and single crystal X-ray diffraction. All compounds were screened for cytotoxicity against the colorectal cancer cell line HCT-116, and 2, 3, 5, 6, 11, and 17 showed remarkable inhibitory activities (IC50: 0.80-2.99 µM), being more active than the positive control 5-fluorouracil (5-FU). The mechanistic study of 2, the most potent compound, showed that it could induce endoplasmic reticulum (ER) stress-mediated apoptosis and improve the sensitivity of HCT-116 cells to 5-FU.

Calcium-sensing receptor acts as an antiviral factor for rotavirus infections and participates in cellular antiviral response.

Objectives: Rotavirus (RV) is one of the most significant pathogens associated with childhood diarrhoeal deaths worldwide. Elevated cytoplasmic calcium is required for RV replication, but the underlying mechanisms responsible for calcium influx remain poorly understood. The Calcium-sensing receptor (CaSR) is an important Ca2+ sensor that regulates the transport of Ca2+ into or out of the extracellular space by affecting the status of Ca2+ ion channels on the membrane of cells. Currently, the function of CaSR in RV replication is unclear. Materials and Methods: We evaluated the mRNA and protein levels of CaSR in RV-infected cells using qRT-PCR and Western blotting, respectively. Furthermore, we silenced or overexpressed CaSR in Caco-2 cells using siRNA or a CaSR gene contained adenovirus (Adv-CaSR). qRT-PCR, plaque assay, and Western blotting were used to determine the synthesis of virus genomic RNA, production of progeny virion, and the levels of viral proteins. The content of Ca2+ in cells was observed under confocal microscopy. Results: Compared with control cells, the RV-infected cells presented significantly decreased CaSR expression. Moreover, adenoviral-mediated over-expression or induction of CaSR by R568 greatly inhibited the RV RNA synthesis, protein expression, and formation of viroplasm plaques, thereby suppressing RV replication. In contrast, CaSR-silenced cells exhibited significantly enhanced RV replication. Compared with the Adv-Control group, the concentration of cytosolic Ca2+ significantly decreased in the Adv-CaSR group. Conclusion: These findings demonstrated that CaSR is a potential target for inhibition of RV replication. Therefore, enhancing the expression of CaSR might protect hosts from RV infections.

Inhibition of NF-κB activation by BAY 11-7821 suppresses the proliferation and inflammation of glioma cells through inducing autophagy.

Background: Gliomas have been known as the most common intracranial malignant tumor, and this kind of tumors cause huge amounts of mortality. The NF-κB inhibitor BAY 11-7821 has been reported as a novel approach in the immunotherapy of lung diseases. However, the functional role of BAY 11-7821 and its association with autophagy in glioma cells have not yet been reported. Methods: In this study, 2 glioma cell lines (U87 and U251) were treated with different doses of BAY 11-7821, or combined with authphagy inhibitor, 3-MA. Afterwards, Transwell assay, CCK-8 assay, EdU staining, Western blot and immunofluorescence assay was used to detected the cell migration, invasion, vability, autophagy in U87 and U251. Results: Our data showed that BAY 11-7821 significantly suppressed the viability, proliferation, migration, and invasion of glioma cells in a dose-dependent manner. At the molecular level, BAY 11-7821 downregulated the protein levels of p-IκBα, p-p65, NLRP3, and p62, and upregulated the protein levels of caspase 3 and Bax, as well as decreased the levels of IL-1ß and IL-18. Results showed BAY 11-7821 enhanced autophagy. While, Pre-treatment with 3-MA, an autophagy inhibitor, obviously reversed the effects of BAY 11-7821 on malignant biological behaviors of glioma cell, inflammation status, and autophagy. Conclusions: In this study, we found that BAY 11-7821 has an effective inhibitive function on malignant biological behaviors by mediating autophagy. Our findings contribute to a better understanding of BAY 11-7821 as a potential anticancer drug in glioma via activating autophagy.

[Effects of chloropicrin fumigation on soil and growth and development of Panax notoginseng].

The continuous cropping obstacle of Panax notoginseng is serious, and effective control measures are lacking. Soil disinfection with chloropicrin(CP) has been proven to be effective in reducing the obstacles to continuous cropping of other crops. In order to ascertain the effect of CP in the continuous cropping of P. notoginseng, this paper explored the influences of CP at different treatment concentrations(0,30,40,50 kg/Mu, 1 Mu≈667 m~2) on soil macro-element nutrients, soil enzyme activity, growth and development of P. notoginseng, and the accumulation of medicinal components. The results showed that CP fumigation significantly increased the content of total nitrogen, alkali-hydrolyzable nitrogen, ammonium nitrogen, nitrate nitrogen, and available phosphorus in the soil, but it had no significant effect on potassium content. The soil protease activity showed a trend of first increasing and then decreasing with the prolonging of the treatment time. Both the soil urease and acid phosphatase activities showed a trend of first decreasing and then increasing with the prolonging of the treatment time. The higher the CP treatment concentration was, the lower the urease and acid phosphatase activities would be in the soil. The protease activity was relatively high after CP40 treatment, which was better than CP30 and CP50 treatments in promoting the nitrogen-phosphorus-potassium accumulation in P. notoginseng. The seedling survival rates after CP0, CP30, CP40, and CP50 tratments in October were 0, 65.56%, 89.44%, and 83.33%, respectively. Compared with the CP30 and CP50 treatments, CP40 treatment significantly facilitated the growth and development of P. notoginseng, the increase in fresh and dry weights, and the accumulation of root saponins. In summary, CP40 treatment accelerates the increase in soil nitrogen and phosphorus nutrients and their accumulation in P. notoginseng, elevates the seedling survival rate of P. notoginseng, enhances the growth and development of P. notoginseng, and promotes the accumulation of medicinal components. CP40 treatment is therefore recommended in production.

Clinical evidence of dietary supplementation with sesame on cardiovascular risk factors: An updated meta-analysis of randomized controlled trials.

The present analysis was to summarize the evidence of the effects of sesame and its derivatives supplementation on cardiovascular disease (CVD) risk factors by performing a meta-analysis of randomized controlled trials (RCTs). Electronic databases were searched from their inception to July 2020. Two investigators independently assessed articles for inclusion, extracted data, and statistical analysis. The quality of included articles was assessed according to the Cochrane risk of bias tool. Major outcomes were synthesized using a random effect model and presented as weighted mean difference and 95% confidence interval. Heterogeneity, subgroup analyses, sensitivity analysis, meta-regression, and publication bias were also conducted. The GRADE approach was used to evaluate the quality of evidence. Overall, 16 trials involving 908 participants were included for statistical pooling. Compared with the control group, sesame intake significantly decreased the levels of total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body weight, body mass index, hip circumference, and waist circumference (P < 0.05). These results were stable in sensitivity analysis, and no significant publication bias was detected. Our findings provided evidence that sesame consumption may reduce the risk of CVD by improving blood lipids, blood pressure, and body weight management. Further large-scale, well-designed RCTs are required to confirm these results.

circRNA_0006470 promotes the proliferation and migration of gastric cancer cells by functioning as a sponge of miR-27b-3p.

Cancer pathogenesis is influenced by epigenetic alterations mediated by circular RNAs (circRNAs). In this study, we aimed to investigate the regulatory mechanisms and cytological function of hsa_circ_0006470/miR-27b-3p in gastric cancer (GC). circRNA and microRNA expressions in cancer cells were measured by the qRT-PCR method. A dual-luciferase reporter assay was performed to validate the binding of hsa_circ_0006470 with miR-27b-3p. hsa_circ_0006470 was silenced in AGS cells, and proliferation, migration, and invasion were tested via the CCK-8 assay and Transwell system, respectively. The autophagy in GC cells was assessed by marker protein detection and transmission electron microscope. The results showed that hsa_circ_0006470 expression was significantly elevated in GC cells, which was mainly distributed in cytoplasmic components and could directly bind with miR-27b-3p in GC cells. Silencing of hsa_circ_0006470 repressed cell proliferation, migration, and invasion, which may be through regulating miR-27b-3p/Receptor tyrosine kinase-like orphan receptor 1 (ROR1). Silencing of hsa_circ_0006470 also elevated LC3II and Beclin-1 and suppressed p62 protein abundances, which subsequently induced autophagy in AGS cells. Furthermore, we found that hsa_circ_0006470 promotes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) expressing by sponging miR-27b-3p. In conclusion, hsa_circ_0006470 promoted GC cell proliferation and migration through targeting miR-27b-3p and suppressing autophagy machinery.

LncRNA LINC00355 promotes EMT and metastasis of bladder cancer cells through the miR-424-5p/HMGA2 axis.

Bladder cancer is a common malignant tumor with a high recurrence rate and mortality, while the detailed mechanisms for bladder cancer progression and metastasis are unknown. Recently, long non-coding RNAs (lncRNAs) have been reported to be involved in the development of cancers. In this study, we aim to investigate the role of lncRNA LINC00355 in bladder cancer progression and metastasis. The association between LINC00355 and the prognosis of bladder cancer patients was determined by Kaplan-Meier survival analysis. Cell migration and invasion ability were detected using the Transwell migration and invasion assay. The relationships of LINC00355, miR-424-5p, and High Mobility Group AT-Hook 2 (HMGA2) were verified through the luciferase assay and RNA pull-down assay. Xenograft tumor was established to evaluate tumor lung metastasis in vivo. qRT-PCR and western blot were used to detect gene expression. LINC00355 was upregulated in bladder cancer patients, especially in patients with higher TNM stage. Elevated LINC00355 was correlated with the poor prognosis of bladder cancer patients. Besides, overexpressed LINC00355 promoted migration, invasion, and epithelial-mesenchymal transition (EMT) ability of bladder cancer cells. Contrarily, decreased LINC00355 suppressed migration, invasion, and EMT ability of bladder cancer cells, and lung metastasis of xenograft tumors. Furthermore, LINC00355 could regulate HMGA2 expression by acting as a sponge for miR-424-5p. Overexpression of HMGA2 induced EMT of bladder cancer cells. Additionally, LINC00355 regulated the migration, invasion, and EMT ability of bladder cancer cells through modulating HMGA2 expression via sponging miR-424-5p. LINC00355 promoted migration, invasion, and EMT ability of bladder cancer through elevating HMGA2 expression via acting as a sponge for miR-424-5p.

MicroRNA 144 inhibits cell migration and invasion and regulates inflammatory cytokine secretion through targeting toll like receptor 2 in non-small cell lung cancer.

INTRODUCTION: MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules involved in modulation of cancer progression. Here, we investigated the possible role of miR-144 in non-small cell lung cancer (NSCLC) development. MATERIAL AND METHODS: The expression of miR-144 and TLR2 in NSCLC tissue and cell lines was determined by quantitative real-time PCR (qPCR). The TargetScan database was used to predict potential target genes of miR-144. Luciferase assay was used to verify the interaction between TLR2 and miR-144. TLR2 protein expression was measured by western blot. The secretion of interleukin (IL)-1ß, IL-6 and IL-8 in A549 cells was detected by an ELISA kit. Cell migration and invasion were evaluated by wound healing assay and transwell assay, respectively. RESULTS: Our results showed that miR-144 was downregulated in NSCLC tissue and cell lines when compared with the normal tissues and cell line (p < 0.05). The protein level of TLR2 in NSCLC tissue and cell lines was significantly higher than that in normal lung tissues. Dual luciferase reporter gene assay showed that miR-144 could bind to the 3'UTR of TLR2 specifically. Up-regulation of miR-144 significantly decreased the expression of TLR2. Up-regulation of miR-144 or down-regulation of TLR2 could decrease cell migration, invasion and secretion of IL-1ß, IL-6 and IL-8 in A549 cells. Moreover, overexpression of TLR2 rescued the inhibitory effects of miR-144 on migration, invasion and inflammatory factor secretion of A549 cells. CONCLUSIONS: miR-144 could inhibit the migration, invasion and secretion of IL-1ß, IL-6 and IL-8 through downregulation of TLR2 expression in A549 cells.

Effects of a Chlorogenic Acid-Containing Herbal Medicine (LASNB) on Colon Cancer.

BACKGROUND: Plant polyphenols, which contain phenolic acids such as chlorogenic acid (CGA), can be used for the treatment of gastrointestinal cancer and have gained increasing attention in recent years. In this study, we explored a novel CGA-containing herbal medicine named LASNB, which was extracted from Lonicera japonica Thunb., Agrimonia eupatoria L., and Scutellaria barbata D.Don. METHODS: CGA in LASNB was analyzed using high-performance liquid chromatography (HPLC). The biological functions and molecular mechanisms of LASNB were investigated in colon cancer cell lines (HCT116, HCT15, and CT26), a normal colon cell line (NCM460), and a CT26 xenograft model. To assess safety, hematological toxicity and pathology of the liver, kidney, and lung were evaluated. RESULTS: LASNB suppressed HCT116, HCT15, and CT26 colon cancer progression by inhibiting proliferation capacity, promoting cell apoptosis, and suppressing cell migration both in vitro and in vivo. Investigation into the underlying molecular mechanism indicated that LASNB suppressed the activation of receptor tyrosine kinase- (RTK-) MEK-ERK and NF-κB pathways. With regard to safety, slight interstitial vascular congestion in the lung was observed, but no severe pathological or hematological toxicity was detected. CONCLUSIONS: We found that LASNB suppressed the progression of colon cancer via the RTK-MEK-ERK and NF-κB pathways, with no severe toxicity observed. Therefore, LASNB has the potential to be used as a supplementary herbal medicine for the treatment of colon cancer.

S-Equol Protects Chondrocytes against Sodium Nitroprusside-Caused Matrix Loss and Apoptosis through Activating PI3K/Akt Pathway.

Osteoarthritis (OA) is a common chronic disease with increasing prevalence in societies with more aging populations, therefore, it is causing more concern. S-Equol, a kind of isoflavones, was reported to be bioavailable and beneficial to humans in many aspects, such as improving menopausal symptoms, osteoporosis and prevention of cardiovascular disease. This study investigated the effects of S-Equol on OA progress in which rat primary chondrocytes were treated with sodium nitroprusside (SNP) to mimic OA progress with or without the co-addition of S-Equol for the evaluation of S-Equol's efficacy on OA. Results showed treatment of 0.8 mM SNP caused cell death, and increased oxidative stress (NO and H2O2), apoptosis, and proteoglycan loss. Furthermore, the expressions of MMPs of MMP-2, MMP-3, MMP-9, and MMP-13 and p53 were increased. The addition of 30 µM S-Equol could lessen those caused by SNP. Moreover, S-Equol activates the PI3K/Akt pathway, which is an upstream regulation of p53 and NO production and is associated with apoptosis and matrix degradation. As a pretreatment of phosphoinositide 3-kinases (PI3K) inhibitor, all S-Equol protective functions against SNP decrease or disappear. In conclusion, through PI3K/Akt activation, S-Equol can protect chondrocytes against SNP-induced matrix degradation and apoptosis, which are commonly found in OA, suggesting S-Equol is a potential for OA prevention.

[Effect of acupuncture on the cognitive function of migraine patients with depression/anxiety disorder].

OBJECTIVE: To observe the effect of five-element acupuncture on the cognitive function repair of migraine patients with depression/anxiety disorder. METHODS: The migraine patients with depression/anxiety disorder (19 cases, 5 cases dropped off) were taken as the observation group, and received five-element acupuncture twice a week for 8 weeks. Healthy subjects (19 cases) were selected by demographic data matching as the control group. The cognitive function was evaluated with the event related potential (ERP) technique, and the latency and amplitude of visual evoked potential P300 were adopted as the observation indexes. The headache days (every 4 weeks), headache intensity [visual analogue scale(VAS) score], and headache impact test-6 (HIT-6) score, Hamilton depression scale (HAMD) score and Hamilton anxiety scale (HAMA) score were used as the observation indexes for curative effect. RESULTS: Before the treatment, latency of target stimulus at Fz [ (417.5±34.3) ms] in the observation group was extended compared with the healthy subjects of the control group [(388.6±42.1) ms, P<0.05]. In the observation group, the latency of each point target stimulus [Fz: (376.1±36.2) ms, F3: (374.8±37.6) ms, F4: (372.0±37.6) ms] after treatment were shorter than those [Fz: (417.5±34.3) ms, F3: (417.4±33.8) ms, F4: (416.0±36.6) ms] before treatment (P<0.05). Before and after treatment, there was no significant difference in the amplitude of each point between the observation group and the control group (P>0.05). In the observation group, the headache days was shorter than that before treatment (P<0.01), and the VAS score, HIT-6 score, HAMD score and HAMA score were all lower than before treatment (P<0.01). CONCLUSION: There are some cognitive impairments in migraine patients with depression/anxiety disorder. Five-element acupuncture not only relieves headache, anxiety and depression effectively, but also improves the activation level of the frontal lobe. It significantly repairs the impaired cognitive function.