Predictors of return to work after spinal surgery : systematic review and Meta-analysis.

PURPOSE: To analyze the situation and influencing factors of patients returning to work after spinal surgery, and to provide reference for clinical intervention measures of patients returning to work after spinal surgery. METHODS: A computer search was conducted in Chinese and English database on the situation and influencing factors of patients returning to work after spinal surgery from the establishment of the database to February 2023. Meta-analysis was performed using RevMan 5.3 and StataMP 17.0 software. RESULTS: A total of 10 literatures were included, involving 11,548 subjects. Meta-analysis results showed that 58% of patients returned to work after spinal surgery [95%CI (0.47-0.69)]. Gender [OR = 2.41, 95%CI (1.58-3.37)], age [OR = 1.32, 95%CI (1.03-1.51)], job nature [OR = 5.94, 95%CI (3.54-9.62)], education level [OR = 0.23, 95%CI (0.06-0.48)], fear of disease progression [OR = 0.82, 95%CI (0.84-0.95)], and social support [OR = 1.21, 95%CI (1.12-1.37)] were the influencing factors for patients returning to work after spinal surgery. CONCLUSION: The rate of patients returning to work after spinal surgery is low, and is affected by many factors. Medical personnel should pay comprehensive attention to the above high-risk groups and give timely intervention and support.

Herpes virus entry mediator signaling blockade produces mortality in neonatal sepsis through induced cardiac dysfunction.

Introduction: Sepsis remains a major source of morbidity and mortality in neonates, and characterization of immune regulation in the neonatal septic response remains limited. HVEM is a checkpoint regulator which can both stimulate or inhibit immune responses and demonstrates altered expression after sepsis. We hypothesized that signaling via HVEM would be essential for the neonatal response to sepsis, and that therefore blockade of this pathway would improve survival to septic challenge. Methods: To explore this, neonatal mice were treated with cecal slurry (CS), CS with Anti-HVEM antibody (CS-Ab) or CS with isotype (CS-IT) and followed for 7-day survival. Mice from all treatment groups had thymus, lung, kidney and peritoneal fluid harvested, weighed, and stained for histologic evaluation, and changes in cardiac function were assessed with echocardiography. Results: Mortality was significantly higher for CS-Ab mice (72.2%) than for CS-IT mice (22.2%). CS resulted in dysregulated alveolar remodeling, but CS-Ab lungs demonstrated significantly less dysfunctional alveolar remodeling than CS alone (MCL 121.0 CS vs. 87.6 CS-Ab), as well as increased renal tubular vacuolization. No morphologic differences in alveolar septation or thymic karyorrhexis were found between CS-Ab and CS-IT. CS-Ab pups exhibited a marked decrease in heart rate (390.3 Sh vs. 342.1 CS-Ab), stroke volume (13.08 CS-IT vs. 8.83 CS-Ab) and ultimately cardiac output (4.90 Sh vs. 3.02 CS-Ab) as well as a significant increase in ejection fraction (73.74 Sh vs. 83.75 CS-Ab) and cardiac strain (40.74 Sh vs. 51.16 CS-Ab) as compared to CS-IT or Sham animals. Discussion: While receptor ligation of aspects of HVEM signaling, via antibody blockade, appears to mitigate aspects of lung injury and thymic involution, stimulatory signaling via HVEM still seems to be necessary for vascular and hemodynamic resilience and overall neonatal mouse survival in response to this experimental polymicrobial septic insult. This dissonance in the activity of anti-HVEM neutralizing antibody in neonatal animals speaks to the differences in how septic cardiac dysfunction should be considered and approached in the neonatal population.

Inonotus obliquus sclerotia epidermis were different from internal tissues in compound composition, antioxidant activity, and associated fungi.

Inonotus obliquus is a medicinal fungus with potential for use in various health applications. To better utilize this fungus, this study focused on epidermis and internal tissues of five sclerotia from different regions in Jilin, Inner Mongolia, and Heilongjiang, examining their polyphenols, polysaccharides, flavonoids, and total triterpenes contents. And evaluated the extracts from sclerotia for their total antioxidant capacity and scavenging ability of DPPH free radicals. The study also isolated the associated fungi from the epidermis and internal tissues of three sclerotia. Results revealed that the polyphenol content was higher in the epidermis than in internal tissue of every sclerotium. However, flavonoid and total triterpenoid content was lower in the epidermis of every sclerotium. The polysaccharide content was no significant in different parts of three sclerotia, but the epidermal polysaccharide content in two sclerotia was significantly higher than in internal tissues. The internal tissue extracts from tested sclerotia exhibited better scavenging ability of DPPH free radicals than those from the epidermis. There was no significant difference in total antioxidant capacity among different parts of three sclerotia, and the internal tissues' total antioxidant capacity in two sclerotia was higher than the epidermis. The number and species of associated fungi in the internal tissues were far less than that in the epidermis. The study suggests separating the epidermis and internal tissue for medicinal use. The research provides insights into the bioactive components and associated fungi of I. obliquus to inform its practical application in medicine.

Nasal splinting and mouth breathing training reduce emergence delirium after endoscopic sinus surgery: a randomized controlled trial.

BACKGROUND: Emergence delirium (ED) is generally occurred after anesthesia associated with increased risks of long-term adverse outcomes. Therefore, this study aimed to evaluate the efficacy of preconditioning with nasal splint and mouth-breathing training on prevention of ED after general anesthesia. METHODS: This randomized controlled trial enrolled 200 adult patients undergoing ESS. Patients were randomized to receive either nasal splinting and mouth breathing training (n = 100) or standard care (n = 100) before surgery. The primary outcome was the occurrence of ED within 30 min of extubation, assessed using the Riker Sedation-Agitation Scale. Logistic regression identified risk factors for ED. RESULTS: Totally 200 patients were randomized and 182 aged from 18 to 82 years with 59.9% of males were included in the final analysis (90 in C-group and 92 in P-group). ED occurred in 16.3% of the intervention group vs. 35.6% of controls (P = 0.004). Male sex, smoking and function endoscopic sinus surgery (FESS) were independent risk factors for ED. CONCLUSIONS: Preoperative nasal splinting and mouth breathing training significantly reduced the incidence of emergence delirium in patients undergoing endoscopic sinus surgery. TRIAL REGISTRATION: ChiCTR1900024925 ( https://www.chictr.org.cn/index.aspx ) registered on 3/8/2019.

Nocardioides potassii sp. nov., isolated from weathered potash tailings soil.

A Gram-positive, aerobic actinomycete, designated strain KLBMP 9356T, was isolated from weathered potash tailings soil sampled in Xuzhou, Jiangsu Province, PR China. The colonies were cream-coloured, convex and rounded. The optimal growth conditions of strain KLBMP 9356T were 1 % (w/v) NaCl, 28 °C and pH 7. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain KLBMP 9356T showed the highest similarity to Nocardioides zhouii CGMCC 1.11084T (98.9 %) and Nocardioides glacieisoli CGMCC 1.11097T (98.7 %). Results from two tree-making algorithms supported the position that strain KLBMP 9356T forms a stable clade with N. zhouii CGMCC 1.11084T and N. glacieisoli CGMCC 1.11097T. Strain KLBMP 9356T exhibited low digital DNA-DNA hybridization values with N. zhouii CGMCC 1.11084T (27.6 %) and N. glacieisoli CGMCC 1.11097T (31.4 %). The average nucleotide identity values between strain KLBMP 9356T and N. zhouii CGMCC 1.11084T and N. glacieisoli CGMCC 1.11097T were 83.8% and 85.9%, respectively. The peptidoglycan in the cell wall of the novel strain was ll-2,6-diaminopimelic acid and the predominant menaquinone was MK-8(H4). The major fatty acids (>10 %) were C17:1ω8c and C18:1ω9c. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, lyso-phospatidylglycerol and phosphatidylinositol. The genomic DNA G+C content was 71.6 mol%. Based on its morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 9356T represents a novel species of the genus Nocardioides, for which the name Nocardioides potassii sp. nov. is proposed. The type strain is KLBMP 9356T (=CGMCC 4.7738T=NBRC 115493T).

Diversity of Endophytic Microbes in Taxus yunnanensis and Their Potential for Plant Growth Promotion and Taxane Accumulation.

Taxus spp. are ancient tree species that have survived from the Quaternary glacier period, and their metabolites, such as taxol, have been used as anticancer drugs globally. Plant-endophytic microbial interaction plays a crucial role in exerting a profound impact on host growth and secondary metabolite synthesis. In this study, high-throughput sequencing was employed to explore endophytic microbial diversity in the roots, stems, and leaves of the Taxus yunnanensis (T. yunnanensis). The analysis revealed some dominant genera of endophytic bacteria, such as Pseudomonas, Neorhizobium, Acidovorax, and Flavobacterium, with Cladosporium, Phyllosticta, Fusarium, and Codinaeopsis as prominent endophytic fungi genera. We isolated 108 endophytic bacteria and 27 endophytic fungi from roots, stems, and leaves. In vitro assays were utilized to screen for endophytic bacteria with growth-promoting capabilities, including IAA production, cellulase, siderophore production, protease and ACC deaminase activity, inorganic phosphate solubilization, and nitrogen fixation. Three promising strains, Kocuria sp. TRI2-1, Micromonospora sp. TSI4-1, and Sphingomonas sp. MG-2, were selected based on their superior growth-promotion characteristics. These strains exhibited preferable plant growth promotion when applied to Arabidopsis thaliana growth. Fermentation broths of these three strains were also found to significantly promote the accumulation of taxanes in T. yunnanensis stem cells, among which strain TSI4-1 demonstrated outstanding increase potentials, with an effective induction of taxol, baccatin III, and 10-DAB contents. After six days of treatment, the contents of these metabolites were 3.28 times, 2.23 times, and 2.17 times the initial amounts, reaching 8720, 331, and 371 ng/g of dry weight of stem cells, respectively. These findings present new insight into the industrialization of taxol production through Taxus stem cell fermentation, thereby promoting the conservation of wild Taxus resources by maximizing their potential economic benefits.

Yinghuangia soli sp. nov., isolated from soil of weathering dolomite in a karst area.

A Gram-stain-positive, aerobic actinomycete strain, designated KLBMP 8922T, was isolated from a soil sample collected from weathering dolomite crust in Guizhou Province, PR China. KLBMP 8922T showed the 16S rRNA gene similarities to Yinghuangia seranimata CCTCC AA 206006T (98.7 %), Yinghuangia catbensis VN07A0015T (98.3 %) and Yinghuangia aomiensis M24DS4T (98.2 %). The taxonomic status of this strain was investigated by using a polyphasic approach. The aerial mycelia of KLBMP 8922T formed spore chains, and spores were cylindrical with smooth surfaces. The whole-cell sugars were ribose, mannose and galactose with traces of glucose and xylose. The diagnostic amino acids of the cell wall were ll-diaminopimelic acid, alanine and glutamic acid. The predominant menaquinones were MK-9(H6) and MK-9(H8). The diagnostic phospholipids were diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositolmannoside, phosphatidylethanolamine, an unidentified phospholipid and an unidentified lipid. The major cellular fatty acids (>10 %) were iso-C15 : 0, iso-C16 : 0 and iso-C16 : 1H. The genomic DNA G+C content was 72.0 mol%. The digital DNA-DNA hybridization (dDDH) value between KLBMP 8922T and Y. seranimata CCTCC AA 206006T was 24.1 %, and the average nucleotide identity (ANI) value was 81.0 %. On the basis of a combination of morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 8922T represents a novel species of the genus Yinghuangia for which the name Yinghuangia soli sp. nov. is proposed. The type strain was KLBMP 8922T (= CGMCC 1.19360T = NBRC 115572T).

Antribacter soli sp. nov., a novel actinobacterium isolated from soils of weathering dolomite.

Strain KLBMP 9083T, a novel actinobacterium, was isolated from weathered soils collected from a karst area in Anshun, Guizhou Province, PR China. The taxonomic position of strain KLBMP 9083T was studied using the polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain KLBMP 9083T formed a stabilized monophyletic clade with its closest relative strain Antribacter gilvus CGMCC 1.13856T (98.4 % 16S rRNA gene sequence similarity). The peptidoglycan hydrolysates contained alanine, glutamic acid, threonine and lysine. The polar lipids were composed of diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an unidentified phosphoglycolipid, an unidentified phospholipid and an unidentified glycolipid. The predominant menaquinones were MK-9(H8) (87.1 %), MK-9(H6) (7.3 %) and MK-9(H4) (5.6 %). The major fatty acids (>10 %) were anteiso-C15 : 0 and iso-C15 : 0. The genomic DNA G+C content was 72.3 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between strain KLBMP 9083T and A. gilvus CGMCC 1.13856T were 23.4 and 79.9 %, respectively. On the basis of morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 9083T represents a novel species of the genus Antribacter, for which the name Antribacter soli sp. nov. is proposed. The type strain is KLBMP 9083T (=CGMCC 4.7737T=NBRC 115577T).

Control of focal adhesion kinase activation by RUNX1-regulated miRNAs in high-risk AML.

We recently described a 16-gene expression signature for improved risk stratification of acute myeloid leukemia (AML) patients called the AML Prognostic Score (APS). A subset of APS-high-risk AML patients showed increased levels of focal adhesion kinase (FAK), encoded by the Protein Tyrosine Kinase 2 (PTK2) gene, which was correlated with RUNX1 mutations. RUNX1 mutant cells are more sensitive to PTK2 inhibitors. As we were not able to detect RUNX1-binding sites in the PTK2 promoter, we hypothesized that RUNX1 might regulate micro(mi)RNAs that repress PTK2, such that loss-of-function RUNX1 mutations would result in reduced miRNA expression and derepression of PTK2. Examination of paired RNA-seq and miRNA-seq data from 301 AML cases revealed two miRNAs that positively correlated with RUNX1 expression, contained RUNX1-binding sites in their promoters and were predicted to target PTK2. We show that the hsa-let7a-2-3p and hsa-miR-135a-5p promoters are regulated by RUNX1, and that PTK2 is a direct target of both miRNAs. Even in the absence of RUNX1 mutations, hsa-let7a-2-3p and hsa-miR-135a-5p regulate PTK2 expression, and reduced expression of these two miRNAs sensitizes AML cells to PTK2 inhibition. These data explain how RUNX1 regulates PTK2, and identify potential miRNA biomarkers for targeting AML with PTK2 inhibitors.

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy.

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both in vitro and in vivo. Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation in vivo. In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

Feedback loop promotes sucrose accumulation in cotyledons to facilitate sugar-ethylene signaling-mediated, etiolated-seedling greening.

De-etiolation is indispensable for seedling survival and development. However, how sugars regulate de-etiolation and how sugars induce ethylene (ET) for seedlings to grow out of soil remain elusive. Here, we reveal how a sucrose (Suc) feedback loop promotes de-etiolation by inducing ET biosynthesis. Under darkness, Suc in germinating seeds preferentially induces 1-amino-cyclopropane-1-carboxylate synthase (ACS7; encoding a key ET biosynthesis enzyme) and associated ET biosynthesis, thereby activating ET core component ETHYLENE-INSENSITIVE3 (EIN3). Activated EIN3 directly inhibits the function of Suc transporter 2 (SUC2; a major Suc transporter) to block Suc export from cotyledons and thereby elevate Suc accumulation of cotyledons to induce ET. Under light, ET-activated EIN3 directly inhibits the function of phytochrome A (phyA; a de-etiolation inhibitor) to promote de-etiolation. We therefore propose that under darkness, the Suc feedback loop (Suc-ACS7-EIN3-|SUC2-Suc) promotes Suc accumulation in cotyledons to guarantee ET biosynthesis, facilitate de-etiolation, and enable seedlings to grow out of soil.

TcMYB29a, an ABA-Responsive R2R3-MYB Transcriptional Factor, Upregulates Taxol Biosynthesis in Taxus chinensis.

Paclitaxel (Taxol), a highly modified diterpene agent mainly obtained from Taxus species, is the most widely used anticancer drug. Abscisic acid (ABA) is a well-known stress hormone that plays important roles in the secondary metabolism of plants, and it can also induce the accumulation of taxol in Taxus cell suspension cultures. However, the mechanism behind the regulation of taxol biosynthesis by ABA remains largely unknown. In previous research, a R2R3 MYB transcription factor (TF) TcMYB29a was observed to show a significant correlation with taxol biosynthesis, indicative of its potential role in the taxol biosynthesis. In this study, the TcMYB29a encoded by its gene was further characterized. An expression pattern analysis revealed that TcMYB29a was highly expressed in the needles and roots. Overexpression of TcMYB29a in Taxus chinensis cell suspension cultures led to an increased accumulation of taxol, and upregulated expression of taxol-biosynthesis-related genes, including the taxadiene synthase (TS) gene, the taxane 5α-hydroxylase (T5OH) gene, and the 3'-N-debenzoyl-2'-deoxytaxol-N-benzoyltransferase (DBTNBT) gene as compared to the controls. Chromatin immunoprecipitation (ChIP) assays, yeast one-hybrid (Y1H) assays, electrophoretic mobility shift assays (EMSAs), and dual-luciferase reporter assays verified that TcMYB29a could bind and activate the promoter of TcT5OH. Promoter sequence analysis of TcMYB29a revealed that its promoter containing an AERB site from -313 to -319 was a crucial ABA-responsive element. Subsequently, the ABA treatment assay showed that TcMYB29a was strongly upregulated at 6 h after ABA pretreatment. Furthermore, TcMYB29a was strongly suppressed at 3 h after the methyl jasmonate (MeJA) treatment and was depressed to the platform at 12 h. Taken together, these results reveal that TcMYB29a is an activator that improves the accumulation of taxol in Taxus chinensis cells through an ABA-medicated signaling pathway which is different from JA-medicated signaling pathways for the accumulation of taxol. These findings provide new insights into the potential regulatory roles of MYBs on the expression of taxol biosynthetic genes in Taxus.

Endophytic fungus Pseudodidymocyrtis lobariellae KL27 promotes taxol biosynthesis and accumulation in Taxus chinensis.

BACKGROUND: Taxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants. RESULTS: Here, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs. CONCLUSIONS: Our results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.

Transversus abdominis plane block provides effective and safe anesthesia in the cesarean section for an amyotrophic lateral sclerosis parturient: A case report.

RATIONALE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with the fatal course of muscle weakness. The published experience of anesthesia management in the cesarean section with ALS parturient is scant. PATIENT CONCERNS: A 34-year-old woman was admitted to our center complaining of obvious dysphagia together with atrophy and weakness of quadriceps at 24 weeks of her pregnancy. Cesarean was planned at 36 weeks' gestation due to the rapid deterioration of the mother. DIAGNOSES: The results of neurological examination, electromyography and spinal magnetic resonance imaging suggested ALS according to the EI Escorial World Federation of Neurology criteria. INTERVENTIONS: Ultrasound-guided transversus abdominis plane block with 0.6 minimum alveolar concentration sevoflurane was used in this ALS parturient during her cesarean section procedure. OUTCOMES: This anesthesia strategy successfully met the demands of the surgery, helped avoid prolonged ventilation and prevent maternal respiratory complications. LESSONS: Transversus abdominis plane block with subanesthetic concentrations of sevoflurane can provide effective and safe anesthesia in the cesarean section for a patient with ALS.

Cochlioquinone derivative CoB1 induces cytostatic autophagy in lung cancer through miRNA-125b and Foxp3.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide, yet no effective medication for this disease is available. Cochlioquinone B derivative (CoB1), purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana, affects the defense against pulmonary pathogens by regulating inflammatory responses. However, the effect of CoB1 on lung cancer and the underlying molecular mechanisms remain unknown. In the present study, we investigate the protective effects of CoB1 on lung cancer and explore its underlying mechanism. METHOD: We examined the inhibitory effect of CoB1 on lung cancer cells (A549 cells) by MTT and colony formation assay. The effect of CoB1 on cytostatic autophagy in lung cancer cells was verified by Western blot, transmission electron microscopy, and confocal microscopy. The differentially expressed miRNAs were identified using quantitative RT-PCR. Luciferase assay and Northern blot were performed to verify the correlation between miRNA-125b and Foxp3. Protein expression in autophagy-related pathways was detected by Western blot. Xenograft tumor models were constructed to explore the inhibitory effect of CoB1 and the role of miRNA-125b as a suppressor in lung cancer in vivo. RESULT: CoB1 inhibited lung cancer cell proliferation by inducing cytostatic autophagy both in vitro and in vivo. CoB1-induced autophagy was related to blocking of the PI3K/Akt1/mTOR signaling pathway. In addition, CoB1 induced miR-125b expression via activating the TAK1/MKK4/JNK/Smad axis, thereby reducing Foxp3 expression and further inducing autophagy. CONCLUSION: This study is the first to report the specific inhibitory function of CoB1 purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana in lung cancer, which may be due to the induction of autophagy. This study provides evidence and novel insights into the anticancer efficacy of CoB1.

A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia.

As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data from 154 AML patients are used to develop a novel AML prognostic score, which is strongly associated with patient outcomes across 620 patients from three independent cohorts, and 42 patients from a prospective cohort. When combined with molecular risk guidelines, the risk score allows for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identify a subset of patients characterized by dysregulated integrin signaling and RUNX1 or TP53 mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase, encoded by PTK2, demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.

Parallel analysis of global garlic gene expression and alliin content following leaf wounding.

BACKGROUND: Allium sativum (garlic) is an economically important food source and medicinal plant rich in sulfides and other protective substances such as alliin, the precursor of allicin biosynthesis. Cysteine, serine and sulfur is the precursor of alliin biosynthesis. However, little is known about the alliin content under abiotic stress or the mechanism by which it is synthesized. RESULTS: The findings revealed that the content of alliin was lowest in the garlic roots, and highest in the buds. Furthermore, alliin levels decreased in mature leaves following wounding. Transcriptome data generated over time after wounding further revealed significant up-regulation of genes integral to the biosynthetic pathways of cysteine and serine in mature garlic leaves. CONCLUSIONS: The findings suggest that differential expression of cysteine, serine and sulfide-related genes underlies the accumulation of alliin and its precursors in garlic, providing a basis for further analyses of alliin biosynthesis.

Therapeutic potential of IBP as an autophagy inducer for treating lung cancer via blocking PAK1/Akt/mTOR signaling.

Lung cancer is the most frequent and fatal malignancy in humans worldwide, yet novel successful drugs for control of this disease are still lacking. Ipomoea batatas polysaccharides (IBPs) have been implicated in inhibiting diverse cancer types, but their functions in mitigating lung cancer are largely unknown. In this study, we identify a role of IBP in inhibiting lung cancer proliferation. We found that IBP significantly impedes the proliferation of lung cancer cells by inducing cytostatic macroautophagy both in vitro and in vivo. Mechanistically, IBP specifically promotes ubiquitination-mediated degradation of PAK1 (p21-activated kinase 1) and blocks its downstream Akt1/mTOR signaling pathway, leading to increased autophagic flux. In lung cancer xenografts in mice, IBP-induced cytostatic autophagy suppresses tumor development. Through site-directed mutational analysis, the underlying signaling augments ubiquitination via PAK1-ubiquitin interaction. Collectively, this work unravels the molecular mechanism underpinning IBP-induced cytostatic autophagy in lung cancer and characterizes IBP as a potential therapeutic agent for lung cancer treatment.

Effect of Heat Treatment on the Anticancer Activity of Houttuynia cordata Thunb Aerial Stem Extract in Human Gastric Cancer SGC-7901 Cells.

Gastric cancer is one of the most common malignant tumors in the world, and prevention through diet is one of the ways to control. Houttuynia cordata thunb.(HCT) is a plant having medicine and food function, has many biological properties. However, the effect of food style on the anticancer activity of HCT is not clear. So, we investigate the effect of heat treatment on anticancer activity of HCT. HCT extracts (heated aerial stem, heated subterraneous stem, heated leaves defined as HAS, HSS, HL, respectively, and not heated defined as NAS, NSS, NL, respectively) were obtained, and their inhibited activity were detected by alamar blue assay. The cell apoptosis was detected by DAPI staining and flow cytometry analysis. Western blot was performed to test the expression of apoptotic related protein. HCT showed the anticancer activity in four human tumor cell lines. Interestingly, heat treatment could increase the anticancer activity. In SCG-7901 cells, heat treatment increased anticancer activity of AS by 2-14 folds and induced apoptosis through regulating the intrinsic signaling pathways. Intriguingly, the caspase nine specific inhibitor blocked AS-reduced cell viability. Heat treatment increased the anticancer activity of HCT, and can be used as a dietary style for prevention of gastric cancer.