MicroRNA-708 emerges as a potential candidate to target undruggable NRAS.

RAS, the most frequently mutated oncogene that drives tumorigenesis by promoting cell proliferation, survival, and motility, has been perceived as undruggable for the past three decades. However, intense research in the past has mainly focused on KRAS mutations, and targeted therapy for NRAS mutations remains an unmet medical need. NRAS mutation is frequently observed in several cancer types, including melanoma (15-20%), leukemia (10%), and occasionally other cancer types. Here, we report using miRNA-708, which targets the distinct 3' untranslated region (3'UTR) of NRAS, to develop miRNA-based precision medicine to treat NRAS mutation-driven cancers. We first confirmed that NRAS is a direct target of miRNA-708. Overexpression of miRNA-708 successfully reduced NRAS protein levels in melanoma, leukemia, and lung cancer cell lines with NRAS mutations, resulting in suppressed cell proliferation, anchorage-independent growth, and promotion of reactive oxygen species-induced apoptosis. Consistent with the functional data, the activities of NRAS-downstream effectors, the PI3K-AKT-mTOR or RAF-MEK-ERK signaling pathway, were impaired in miR-708 overexpressing cells. On the other hand, cell proliferation was not disturbed by miRNA-708 in cell lines carrying wild-type NRAS. Collectively, our data unveil the therapeutic potential of using miRNA-708 in NRAS mutation-driven cancers through direct depletion of constitutively active NRAS and thus inhibition of its downstream effectors to decelerate cancer progression. Harnessing the beneficial effects of miR-708 may therefore offer a potential avenue for small RNA-mediated precision medicine in cancer treatment.

Isolation and identification of chemical constituents in the above-ground part of the plant Achyranthes bidentata BI / 国际药学研究杂志

Objective: To investigate the chemical constituents in the the above-ground part of the plant Achyranthes bidentata Bl. in Amarathaceae. Methods: The raw materials were extracted by heating with 70% ethanol, and the extract was prepared by column chromatography on Diaion HP-20, MCI Gel CHP-20P, Toyopearl HW-40, Sephadex LH-20, ODS and silica gel, coupled with the semi-preparative HPLC, to isolate the chemical constituents. The isolated compounds were identified according to their MS, 1H NMR and 13C NMR data. Results: Twenty one compounds were isolated and identified: haploperoside A(1), sweroside(2), 1'-O-benzyl-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside(3), 2-ethyl-3-methyl-maleimide-N-β-D-glucopyranoside(4), 3-eth- ylidene-4-methyl-2, 5-pyrrolidinedione(5), methyl-5-hydroxy-2-pyridinecarboxylate(6), pericampylinone A(7), syringaresinol(8), episyringaresinol(9), methyl 3, 4-dihydroxybenzoate(10), 4-hydroxyphenylacetone(11), 3, 4-dihydroxyphenylacetic acid methyl ester(12), 2-(4-hydroxyphenyl)-ethanol(13), homovanillyl alcohol(14), dihydrosinapyl alcohol(15), 4-hydroxybenzoic acid (16), caffeic acid(17), 3-(4-hydroxy-3, 5-dimethoxyphenyl)propane-1, 2-diol(18), methyl(E)-3-(4-hydroxyphenyl)acrylate (19), trans-ferulic acid(20)and vanillic acid(21). Conclusion: Compounds 1-7 and 9-19 were isolated from the title plant for the first time.

Two new monoterpenoids of Zingiber officinale peel / 药学学报

The chemical constituents of Zingiber officinale peel were isolated and purified by various chromatographic separation techniques such as Diaion HP-20, MCI Gel CHP-20, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. Seven terpenoids were identified by physicochemical properties and spectral data: (4R,6S)-1-(hydroxymethyl)-5,5-dimethylbicyclo[3.1.1]hept-2-en-4-ol (1), 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3,4-diol (2), 3,5,6-trihydroxy-7-megastigmen-9-one (3), 3-(3-hydroxybutyl)-2,4,4-trimethyl-2,5-cyclohexadien-1-one (4), angelicoidenol (5), grasshopper ketone (6), and dihydrophaseic acid (7), in which compounds 1, 2 are new compounds, named: (4R,6S)-1-(hydroxymethyl)-5,5-dimethylbicyclo[3.1.1]hept-2-en-4-ol and 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3,4-diol, and compounds 3-7 were obtained from this plant for the first time.

Involvement of acid-sensing ion channel 1a in functions of cultured human retinal pigment epithelial cells / 华中科技大学学报（医学）（英德文版）

In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space (SRS) under pathological conditions such as age-related macular degeneration (AMD). Although it is well known that many transporters in the retinal pigment epithelium (RPE) cells can maintain pH homeostasis efficiently, other receptors in RPE may also be involved in sensing acidosis, such as acid-sensing ion channels (ASICs). In this study, we investigated whether ASIC1a was expressed in the RPE cells and whether it was involved in the function of these cells. Real-time RT-PCR and Western blotting were used to analyze the ASIC1a expression in ARPE-19 cells during oxidative stress induced by hydrogen peroxide (H(2)O(2)). Furthermore, inhibition or over-expression of ASIC1a in RPE cells was obtained using inhibitors (amiloride and PCTx1) or by the transfection of cDNA encoding hASIC1a. Cell viability was determined by using the MTT assay. The real-time RT-PCR and Western blotting results showed that both the mRNA and protein of ASIC1a were expressed in RPE cells. Inhibition of ASICs by amiloride in normal RPE cells resulted in cell death, indicating that ASICs play an important physiological role in RPE cells. Furthermore, over-expression of ASIC1a in RPE cells prolonged cell survival under oxidative stress induced by H(2)O(2). In conclusion, ASIC1a is functionally expressed in RPE cells and may play an important role in the physiological function of RPE cells by protecting them from oxidative stress.

Involvement of acid-sensing ion channel 1a in functions of cultured human retinal pigment epithelial cells / 华中科技大学学报（医学）（英德文版）

In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space (SRS) under pathological conditions such as age-related macular degeneration (AMD). Although it is well known that many transporters in the retinal pigment epithelium (RPE) cells can maintain pH homeostasis efficiently, other receptors in RPE may also be involved in sensing acidosis, such as acid-sensing ion channels (ASICs). In this study, we investigated whether ASIC1a was expressed in the RPE cells and whether it was involved in the function of these cells. Real-time RT-PCR and Western blotting were used to analyze the ASIC1a expression in ARPE-19 cells during oxidative stress induced by hydrogen peroxide (H(2)O(2)). Furthermore, inhibition or over-expression of ASIC1a in RPE cells was obtained using inhibitors (amiloride and PCTx1) or by the transfection of cDNA encoding hASIC1a. Cell viability was determined by using the MTT assay. The real-time RT-PCR and Western blotting results showed that both the mRNA and protein of ASIC1a were expressed in RPE cells. Inhibition of ASICs by amiloride in normal RPE cells resulted in cell death, indicating that ASICs play an important physiological role in RPE cells. Furthermore, over-expression of ASIC1a in RPE cells prolonged cell survival under oxidative stress induced by H(2)O(2). In conclusion, ASIC1a is functionally expressed in RPE cells and may play an important role in the physiological function of RPE cells by protecting them from oxidative stress.

Analysis of prognostic factors in patients with locoregional recurrence of esophageal carcinoma after curative treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this paper was to evaluate the treatment outcome of multimodal treatment for 196 patients with locoregional recurrent esophageal cancer after curative treatment and to determine the prognostic factors of recurrence.</p><p><b>METHODS</b>One hundred and ninety six patients with locoregional recurrent esophageal cancer curatively treated in our hospital were included in this study. Kaplan-Meier method was used to analyze the survival rate. Log rank test was used to evaluate the difference between the groups. Multivariate survival analysis was conducted using a Cox proportional hazard regression model with a backward stepwise procedure.</p><p><b>RESULTS</b>The overall 1-, 2- and 3-year survival rates were 29.8%, 5.9% and 4.0%, respectively, with a median survival time of 8.0 months. The univariate analysis showed that ECOG PS, the interval between initial treatment and recurrence, the regimens of initial treatment and retreatment were independent prognostic factors. The multivariate analysis showed that the regimens of initial treatment and retreatment were independent prognostic factors. Retreatment methods significantly influenced the survival. The median survival time of chemoradiotherapy, radiation therapy alone, chemotherapy alone, EGFR-TKI and best supportive care were 13.0, 7.0, 6.0, 4.0 and 3.0 months, respectively (P = 0.000).</p><p><b>CONCLUSIONS</b>The prognosis of patients with locoregional recurrent esophageal cancer after curative treatment is poor. The main prognostic factors are the regimens of initial treatment and retreatment. Multimodal treatment including radiotherapy and chemotherapy may improve the long-term survival of the patients.</p>

SOCS3: a potential therapeutic target for many human diseases / 药学学报

SOCS3 has significant regulation effects in cell signal transduction pathways, which can be induced by many kinds of cytokines and proinflammatory factors. After being studied for years, the effect of SOCS3 has become clear in maintaining physiological functions and affecting histopathologic changes in human tissues. This review presents the role of SOCS3 in the occurrence, development, diagnosis and treatment of human diseases, such as inflammation, virus infection, obesity and tumor. As abnormal levels or impaired function of SOCS3 were reported in the onset and development of disease, SOCS3 can be considered as a bio-marker to diagnose and predict prognosis of some disorders, and as a therapeutic target for certain diseases.

The effect of rhubarb ethanol-extract on hyperlipidemia and liver fatty in rabbits / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of rhubarb ethanol-extract on hyperlipidemia and liver fatty in rabbits.</p><p><b>METHODS</b>Thirty healthy male white rabbits were divided randomly into five groups, six rabbits in each group. The rabbits in control group were fed with common forage. The rabbits in model group were fed with high lipid forage. The rabbits in three different rhubarb groups were fed with high lipid forage and treated with different level rhubarb ethanol-extract (REE). In the process of experiment, periodically measured serology index of the rabbits and observed common physiology index. The rabbits were killed at the end of tenth week, liver fatty degeneration degree and liver coefficient were measured and compared.</p><p><b>RESULTS</b>REE could decrease serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and increase serum high density lipoprotein cholesterol (HDL-C), and reduce liver fatty de generation and protect liver cell function. And the dose-effect relation was showed among different dose REE groups.</p><p><b>CONCLUSION</b>REE can significantly reduce blood lipid, prevent and treat hyperlipidemia and liver fatty.</p>

Effect of N-tosyl-L-phenylalnylchloromethyl ketone and dexamethasone on expression of nuclear transcription factor-kappaB in childhood acute lymphoblastic leukemia and its significance / 中国实验血液学杂志

In order to investigate the effect of N-tosyl-L-phenylalnylchloromethyl ketone (TPCK) and dexamethasone (Dex) on expression of nuclear transcription factor-kappaB (NF-kappaB) in childhood acute lymphoblastic leukemia (ALL) and its significance, so as to provide the experimental basis for corresponding clinical treatment of ALL, in which NF-kappaB is taken as a target. The biotin-streptavidin method was used to detect the expression of NF-kappaB P65 protein and the effects of TPCK and Dex at clinically relevant dosage on activity of NF-kappaB P65 protein in 20 childhood ALL patients. The results indicated that the expression of NF-kappaB P65 protein was strongly diminished and reached to negative level at 2 hours by treatment with 40 micromol/L TPCK, the positive expression of NF-kappaB P65 protein was (2.5 +/- 1.6)%. TPCK had a time-dependent inhibitory effect on ALL cells cultured in vitro. The expression of NF-kappaB P65 protein in ALL cells was strongly inhibited by clinically relevant concentration of dexamethasone 5.0 microg/ml for 24 hours in vitro. The positive expression was (25.0 +/- 3.0)%, there was significant difference, as compared with untreated ALL cells (T=55, P<0.01). It is concluded that TPCK and Dex can inhibit NF-kappaB activity. Inhibition of NF-kappaB activity may be one of the effect mechanism of dexamethasone on ALL cells. Inhibition of NF-kappaB conduction pathway may have a significant value in childhood ALL treatment.

Pathogenic Distribution and Intervention Strategy of Nosocomial Infection in Tumor Department / 中华医院感染学杂志

OBJECTIVE To approach the pathogenic distribution of nosocomial infection and drug-resistance in tumor department to formulate the intervention strategy.METHODS Prospective monitoring and retrospective investigation were performed to analyze the 198 cases of nosocomial infection in tumor department.RESULTS The lower respiratory tract infection was the main infection in tumor department,accounted for 68.2%.The urinary tract infection rated the second,accounted for 16.7%.Pathogenic bacteria mainly included Pseudomonas aeruginosa(20.2%),Klebsiella pneumoniae(19.2%),Escherichia coli(16.2%),Staphylococcus aureus(10.6%),etc.Above pathogenic bacteria were all multidrug-resistant.Detection rate of extended spectrum ?-lactamases(ESBLs) producing Enterobacteriaceae strains was 45.7%.Detection rate of meticillin-resistant staphylococci(MRS) was 40.6%.CONCLUSIONS The drug-resistance status of nosocomial infection is very serious in tumor department.Comprehensive intervention strategy should be adopted to decrease the infection rate.