Neoadjuvant chemoimmunotherapy cycle number selection for non-small cell lung cancer and clinical outcomes: a real-world analysis.

Objectives: Neoadjuvant chemoimmunotherapy is the optimal choice in the treatment of NSCLC; however, the optimal number of therapeutic cycles remains unclear. The primary aim of this study was to determine the optimal number of neoadjuvant therapeutic cycles in NSCLC. Methods: This study was a real-world clinical analysis that included patients who received neoadjuvant chemoimmunotherapy followed by surgery from January 2020 to August 2022. Patients were divided into two groups based on the number of therapeutic cycles: 2-cycle group and 3-4-cycles group. The primary endpoint was the major pathological response (MPR) rate. Results: A total of 251 patients were included: 150 in the 2-cycle group and 101 in the 3-4-cycles group. Baseline characteristics were well-balanced between the groups. The MPR in the 2-cycle group was 57.3% and not significantly different from that of 57.4% in the 3-4-cycles group (p=0.529). Thirty-two patients (31.7%) in the 3-4-cycles group underwent surgery > 42 days after the final cycle of neoadjuvant therapy, significantly more than the 24 patients (16.0%) in the 2-cycle group (p=0.003). The incidence of adverse events related to neoadjuvant therapy was higher in the 3-4-cycles vs 2-cycle groups (72.3% versus 58.0%, respectively; p=0.021), while the 2-cycle group had a higher rate of postoperative morbidities (28.0% versus 12.9%, respectively; p=0.004). Additionally, for patients with ≤ 44.2% regression in diameter on computed tomography after two cycles of treatment, the MPR rate was higher in the 3-4-cycles vs 2-cycle group (47.3% versus 29.9%, respectively; p=0.048). For cases with programmed death-ligand 1 expression, regarding tumor proportion score ≤ 10%, 3-4 cycles of neoadjuvant treatment increased the MPR rate compared with 2 cycles (37.5% versus 9.5%, respectively; p=0.041). Conclusion: Our data support the positive role of chemoimmunotherapy in the neoadjuvant treatment of NSCLC. Extending to 3-4 cycles instead of 2 cycles of neoadjuvant chemoimmunotherapy may improve the safety of surgery and result in a lower incidence of postoperative morbidities; however, the MPR rate may not increase significantly. CT re-evaluation during treatment and PD-L1 expression at initial diagnosis are potential indicators to guide the choice of the number of therapeutic cycles.

Challenging routine: technical difficulties and solutions of endoscopic thyroidectomy via a combined transoral and breast approach - a case-series and learning curve.

OBJECTIVE: Conventional cervical lymph node dissection often leaves large surgical scars, which seriously compromises the postoperative aesthetic effect and can affect the quality of life of patients. In this study, the safety and feasibility of robotic-assisted endoscopic thyroidectomy with central neck dissection (CND) and lateral neck dissection (LND) via a combined transoral and breast approach are discussed in detail. MATERIALS AND METHODS: A retrospective analysis was made of the data of 26 patients with stage cN1b papillary thyroid carcinoma who were admitted to the Thyroid Surgery Department of the Hunan Cancer Hospital from March 2021 to September 2022 and who underwent robotic-assisted endoscopic thyroidectomy with LND via a combined transoral and breast approach. The demographic data, surgical indicators, postoperative data, and the postoperative complication rate of the patients were analyzed, and the learning curve was analyzed by cumulative summation. RESULTS: All the patients underwent endoscopic surgery without any conversion to open surgery. The mean operation time was 313.7±50.3 min and the mean number of total positive/retrieved lymph nodes was 11.2±8.1/36.8±13.7. Two patients developed temporary laryngeal recurrent nerve palsy and three patients developed temporary hypoparathyroidism, all of whom recovered within 3 months postoperatively. No tumor recurrence occurred during follow-ups that ranged from 6 to 24 months. The mean postoperative quality of life (QOL) score was 189.1±118.2, test results ranging from 0 to 1300 with a lower score indicating a higher QOL, and the aesthetic satisfaction score was 4.2±0.7, test scores ranging from 0 to 5 with higher scores indicate higher satisfaction. The turning point of the learning curve was in the 11th case. CONCLUSIONS: The robotic-assisted endoscopic thyroidectomy with CND and LND via a combined transoral and breast approach is safe and feasible, and the improved cosmetic effect is remarkable, which is conducive to improving the postoperative QOL of patients. It provides a new surgical option for patients.

Perioperative outcomes of neoadjuvant chemotherapy plus camrelizumab compared with chemotherapy alone and chemoradiotherapy for locally advanced esophageal squamous cell cancer.

Purpose: Neoadjuvant chemoimmunotherapy (nCIT) is becoming a new therapeutic frontier for resectable esophageal squamous cell carcinoma (ESCC); however, crucial details and technical know-how regarding surgical techniques and the perioperative challenges following nCIT remain poorly understood. The study investigated and compared the advantages and disadvantages of esophagectomy following nCIT with neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT). Methods: We retrospectively analyzed data of patients initially diagnosed with resectable ESCC at clinical stage T2-4N+ and received neoadjuvant therapy followed by esophagectomy at the Hunan Cancer Hospital between October 2014 and February 2021. Patients were divided into three groups according to neoadjuvant treatment: (i) nCIT; (ii) nCT; and (iii) nCRT. Results: There were 34 patients in the nCIT group, 97 in the nCT group, and 31 in the nCRT group. Compared with nCT, nCIT followed by esophagectomy achieved higher pathological complete response (pCR; 29.0% versus 4.1%, p<0.001) and major pathological response (MPR; 52.9% versus 16.5%, p<0.001) rates, more resected lymph nodes during surgery (25.06 ± 7.62 versus 20.64 ± 9.68, p=0.009), less intraoperative blood loss (200.00 ± 73.86 versus 266.49 ± 176.29 mL, p=0.035), and comparable results in other perioperative parameters. Compared with nCRT, nCIT achieved similar pCR (29.0% versus 25.8%) and MPR (52.9% versus 51.6%, p=0.862) rates, with significantly more lymph nodes resected during surgery (25.06 ± 7.62 versus 16.94 ± 7.24, p<0.001), shorter operation time (267.79 ± 50.67 versus 306.32 ± 79.92 min, p=0.022), less intraoperative blood loss (200.00 ± 73.86 versus 264.53 ± 139.76 mL, p=0.022), and fewer ICU admissions after surgery (29.4% versus 80.6%, p<0.001). Regarding perioperative adverse events and complications, no significant statistical differences were detected between the nCIT and the nCT or nCRT groups. The 3-year overall survival rate after nCIT was 73.3%, slightly higher than 46.1% after nCT and 39.7% after nCRT, with no statistically significant differences (p=0.883). Conclusions: This clinical analysis showed that nCIT is safe and feasible, with satisfactory pCR and MPR rates. Esophagectomy following nCIT has several perioperative advantages over nCT and nCRT, with comparable perioperative morbidity and mortality. The long-term survival benefits after nCIT still requires further investigation.

Delayed complications of intradural cement leakage after percutaneous vertebroplasty: A case report.

BACKGROUND: Intradural cement leakage following percutaneous vertebroplasty is a rare but acute and devastating complication that usually requires emergent treatment. Here, we report a delayed complication of intradural leakage after percutaneous vertebroplasty. CASE SUMMARY: A 71-year-old female patient with an L1 osteoporotic compression fracture underwent percutaneous vertebroplasty in 2014. She was referred to our hospital 5 years later due to complaints of progressive weakness and numbness in both legs combined with urinary incontinence and constipation. Initially, she was suspected to have a spinal meningioma at the level of L1 according to imaging examinations. Postoperative pathological tests confirmed that cement had leaked into the dura during the first percutaneous vertebroplasty. CONCLUSION: Guideline adherence is essential to prevent cement from leaking into the spinal canal or even the dura. Once leakage occurs, urgent evaluation and decompression surgery are necessary to prevent further neurological damage.

TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation.

Osteosarcoma (OS), the most common primary malignancy of the bone, has a poor prognosis due to its high mortality rate and high potential for metastasis. Thus, it is urgently necessary to explore functional molecular targets of therapeutic strategies for osteosarcoma. Here, we reported that TIPE1 expression was decreased in osteosarcoma tissues compared to normal and adjacent nontumor tissues, and its expression was negatively related to tumor stage and tumor size. Functional assays showed that TIPE1 inhibited osteosarcoma carcinogenesis and metastatic potential both in vivo and in vitro. Furthermore, we investigated that the STAT3 signaling pathway was significantly downregulated after TIPE1 overexpression. Mechanistically, TIPE1 bind to the catalytic domain of PRMT1, which deposits an asymmetric dimethylarginine (ADMA) mark on histone/non-histone proteins, and thus inhibited PRMT1 mediated STAT3 methylation at arginine (R) residue 688. This abolished modification decreased STAT3 transactivation and expression, by which subsequently suppressed osteosarcoma malignancy. Taken together, these data showed that TIPE1 inhibits the malignant transformation of osteosarcoma through PRMT1-mediated STAT3 arginine methylation and ultimately decreases the development and metastasis of osteosarcoma. TIPE1 might be a potential molecular therapeutic target and an early biomarker for osteosarcoma diagnosis.

Effect of CDCA5 on Proliferation and Metastasis of Triple Negative Breast Cancer Cells under shRNA Interference Technology.

Objective: It was to explore the effect of cell division cycle associated 5 (CDCA5) under shRNA interference on proliferation and metastasis of triple negative breast cancer (TNBC) cells. Methods: MDA-ME-231 and BT549 cells were selected as the research objects. According to the different interference methods and CDCA5 interference sequences, they were divided into the interference group 1MDA-ME-231, the interference group 2MDA-ME-231, the interference group 1BT549, the interference group 2BT549 (using shRNA technology), the control group MDA-ME-231, and the control group BT549 (breast cancer cells under normal culture conditions). MCF10A cells were routinely cultured as the negative control group to analyze the effect of CDCA5 expression on the proliferation and migration of cancer cells. Results: The expression of CDCA5 protein in MDA-ME-231 and BT549 cells in control group was significantly higher than that in negative control group (P < 0.05). Compared with the control group, the inhibition rates of CDCA5 expression in 1MDA-ME-231, 2MDA-ME-231, 1BT549, and 2BT549 cells in the interference group were 39.01%, 42.98%, 49.57%, and 60.98%, respectively (P < 0.05). From 12 h, the proliferation level of TNBC cells at different culture time was lower than that of the control group (P < 0.05). Compared with the number of staining cells in the control group, the positive staining cells in 1MDA-ME-231 (61.42%), 2MDA-ME-231 (72.06%), 1BT549 (52.53%), and 2BT549 (59.65%) in the interference group were significantly decreased (P < 0.05). Conclusion: The results show that the expression of CDCA5 in TNBC is increased, which plays an important role in the proliferation and migration of cancer cells. shRNA interference technology can knock down the expression of CDCA5 and inhibit its "promoting cancer" effect.

Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR.

Cholangiocarcinoma is a relatively rare neoplasm with increasing incidence. Although chemotherapeutic agent such as gemcitabine has long been used as standard treatment for cholangiocarcinoma, the interindividual variability in target and drug sensitivity and specificity may lead to therapeutic resistance. In the present study, we found that photodynamic therapy (PDT) treatment inhibited gemcitabine-resistant cholangiocarcinoma cells via repressing cell viability, enhancing cell apoptosis, and eliciting G1 cell cycle arrest through modulating Cyclin D1 and caspase 3 cleavage. In vivo, PDT treatment significantly inhibited the growth of gemcitabine-resistant cholangiocarcinoma cell-derived tumors. Online data mining and experimental analyses indicate that KLF10 expression was induced, whereas EGFR expression was downregulated by PDT treatment; KLF10 targeted the EGFR promoter region to inhibit EGFR transcription. Under PDT treatment, EGFR overexpression and KLF10 silencing attenuated the anti-cancer effects of PDT on gemcitabine-resistant cholangiocarcinoma cells by promoting cell viability, inhibiting apoptosis, and increasing S phase cell proportion. Importantly, under PDT treatment, the effects of KLF10 silencing were significantly reversed by EGFR silencing. In conclusion, PDT treatment induces KLF10 expression and downregulates EGFR expression. KLF10 binds to EGFR promoter region to inhibit EGFR transcription. The KLF10/EGFR axis participates in the process of the inhibition of PDT on gemcitabine-resistant cholangiocarcinoma cells.

Degradation of ammonia gas by Cu2O/{001}TiO2 and its mechanistic analysis.

A heterogeneous composite catalyst Cu2O/{001}TiO2 was successfully prepared by the impregnation-reduction method. With ammonia as the target pollutant, the degradation performance and degradation mechanism analysis of the prepared composite catalyst were investigated, providing technology for the application of photocatalysis technology in ammonia treatment reference. The catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), specific surface area (BET), fluorescence spectrum (PL) and UV-visible absorption (UV-Vis). The results showed: compared with single {001}TiO2, the addition of Cu2O to form a composite catalyst can reduce the recombination of electron-hole pairs, resulting in increased absorption intensity in the visible light range, decreased band gap width, and finally improved the degradation performance. When the composite ratio is 1 : 10, the specific surface area is the largest, which is 72.51 m2 g-1, and the degradation rate of ammonia is also the highest maintained at 85%. After repeated use for 5 times, the degradation rate of ammonia decreases gradually due to the loss of catalyst and photo-corrosion. In the whole reaction process, surface adsorbed water and associated hydroxyl radical participate in the ammonia degradation reaction, and finally form free hydroxyl radical and NO3 -. It provides some theoretical support for ammonia gas treatment, which is of great significance to protect the environment.

Transoral endoscopic thyroidectomy vestibular approach in a patient with Class III goitre (operative steps and video).

Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has recently become a hot research topic due to the advantage of leaving no scar, but, according to most centers, its indication is restricted to the size of thyroid gland. Here we report a case of a female patient with Class III goitre who successfully underwent TOETVA (video attached). A 53-year-old woman with a previous history of chest keloidosis presented with a history of neck swelling for 3 years and was diagnosed as Hashimoto's thyroiditis with no nodules. The patient insisted that she undergo a TOETVA procedure in our hospital. Compared to the traditional TOETVA, several techniques were applied in this operation to ensure the resection and removal of the thyroid gland: with the dissection of the mental nerve and using the lateral approach to the thyroid gland. The total volume of thyroid gland was 205 mL. The operating time was 195 min. No complications were incurred. The numbness of the lip and chin was measured by the "two-points discrimination" method with several aspects (touch, pain, temperature) at different times to evaluate mental nerve injury. She felt the numbness during the first operative day but it was almost completely relieved in the third postoperative month. To our knowledge, this is the largest thyroid gland reported removed with TOETVA procedure. By carefully designing the operative steps, it is feasible to use the transoral approach in patients who have a benign thyroid disease with a Class III goitre if the patient strongly desires that operation.

Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non-high-incidence area.

BACKGROUND: Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non-high-incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. METHODS: We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40-74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. RESULTS: Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C-index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high-risk and low-risk group divided based on score from the nomogram predicted a significantly distinct detection rate. CONCLUSION: The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non-high-risk areas, thus reducing the incidence of UGC by improving the UGPL detection.

Integrative Bioinformatics Approaches to Screen Potential Prognostic Immune-Related Genes and Drugs in the Cervical Cancer Microenvironment.

In developing countries, cervical cancer is still the major cause of cancer-related death among women. To better understand the correlation between tumor microenvironment (TME) and prognosis of cervical cancer, we screened 1367 differentially expressed genes (DEGs) of cervical cancer samples in The Cancer Genome Atlas (TCGA) database using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm-derived immune scores. Then, we extracted 401 tumor immune microenvironment (TIME)-related DEGs that related to patients' survival outcomes. Protein-protein interaction (PPI) network and functional enrichment analysis revealed that the prognostic genes mainly participated in myeloid leukocyte activation, adaptive immune response regulation, and receptor signaling pathways. A total of 79 key prognostic DEGs were obtained through PPI network. A TF-lncRNA-miRNA-mRNA regulatory network was constructed to explore the potential regulatory mechanism. 4 genes (CCR7, PD-1, ZAP70, and CD28) were validated in another independent cohort of cervical cancer from the Gene Expression Omnibus (GEO) database. Finally, potential drugs for key prognostics DEGs were predicted using DrugBank. In conclusion, we obtained a list of potential prognostic TIME-related genes and potential predicted drugs by integrative bioinformatics approaches. A comprehensive understanding of prognostic genes within the TIME may provide new strategies for cervical cancer treatment.

Dose preservation of ligament flavum really help prevent postoperative epidural fibrosis and improve outcome in microdiscectomy?

OBJECTIVE: A prospective, randomized, controlled clinical study was conducted with surgery performed by the same surgeon. The aim was to present a new technique for preserving the ligament flavum during lumbar microdiscectomy, and to evaluate whether this helps prevent postoperative fibrosis and improve outcome. METHODS: From January to December 2017, 251 patients with indication for microdiscectomy were randomly divided into test group using ligament flavum preservation technique and control group using conventional procedures. Visual analogue scale (VAS) scores and Oswestry Disability Index (ODI) were assessed before the surgery, and 3 days, 1 month, 6 months, 1 year and 2 years after the operation respectively. The grade of epidural fibrosis on MRI after 6 months was evaluated by two radiologists independently and double-blindly. RESULTS: Both groups' VAS and ODI were significantly improved after surgery, but there was no significant difference between two groups at 3d and 1 month after operation. The grade of epidural fibrosis in test group was significantly lower than that in control group at 6 months postoperative. The VAS and ODI were significantly lower in test group than that in control group at 6 months,1 year and 2 years after operation. CONCLUSION: Preservation of more ligament flavum is practicable during the procedure of microdiscectomy. It can prevent postoperative epidural fibrosis, and is helpful to achieve a better clinical outcome.

Sinomenine Inhibits Non-Small Cell Lung Cancer via Downregulation of Hexokinases II-Mediated Aerobic Glycolysis.

BACKGROUND: Addiction to aerobic glycolysis is a common metabolic phenotype in human non-small cell lung cancer (NSCLC). The natural product Sinomenine (Sin) exhibits significant anti-tumor effects in various human cancers. However, the underlying mechanism remains elusive. METHODS: The inhibitory effect of Sin on NSCLC cells was determined by MTS and soft agar assays. The glycolysis efficacy of NSCLC cells was examined by glucose uptake and lactate production. The activation of Akt signaling and the protein level of hexokinases II (HK2) were examined by immunoblot (IB), qRT-PCR, and immunohistochemical staining (IHC). The in vivo anti-tumor effect of Sin was validated by the xenograft mouse model. RESULTS: We showed that HK2 is highly expressed in NSCLC tissues and cell lines. Depletion of HK2 suppressed cell viability, anchorage-independent colony formation, and xenograft tumor growth. Sinomenine exhibited a profound inhibitory effect on NSCLC cells by reducing HK2-mediated glycolysis both in vitro and in vivo. Ectopic overexpression of HK2 compromised these anti-tumor efficacies in sinomenine-treated NSCLC cells. Moreover, we revealed that sinomenine decreased Akt activity, which caused the down-regulation of HK2-mediated glycolysis. Knockdown of Akt reduced HK2 protein level and impaired glycolysis. In contrast, overexpression of constitutively activated Akt1 reversed this phenotype. CONCLUSION: This study suggests that targeting HK2-mediated aerobic glycolysis is required for sinomenine-mediated anti-tumor activity.

IbBBX24 Promotes the Jasmonic Acid Pathway and Enhances Fusarium Wilt Resistance in Sweet Potato.

Cultivated sweet potato (Ipomoea batatas) is an important source of food for both humans and domesticated animals. Here, we show that the B-box (BBX) family transcription factor IbBBX24 regulates the jasmonic acid (JA) pathway in sweet potato. When IbBBX24 was overexpressed in sweet potato, JA accumulation increased, whereas silencing this gene decreased JA levels. RNA sequencing analysis revealed that IbBBX24 modulates the expression of genes involved in the JA pathway. IbBBX24 regulates JA responses by antagonizing the JA signaling repressor IbJAZ10, which relieves IbJAZ10's repression of IbMYC2, a JA signaling activator. IbBBX24 binds to the IbJAZ10 promoter and activates its transcription, whereas it represses the transcription of IbMYC2 The interaction between IbBBX24 and IbJAZ10 interferes with IbJAZ10's repression of IbMYC2, thereby promoting the transcriptional activity of IbMYC2. Overexpressing IbBBX24 significantly increased Fusarium wilt disease resistance, suggesting that JA responses play a crucial role in regulating Fusarium wilt resistance in sweet potato. Finally, overexpressing IbBBX24 led to increased yields in sweet potato. Together, our findings indicate that IbBBX24 plays a pivotal role in regulating JA biosynthesis and signaling and increasing Fusarium wilt resistance and yield in sweet potato, thus providing a candidate gene for developing elite crop varieties with enhanced pathogen resistance but without yield penalty.

A non-tandem CCCH-type zinc-finger protein, IbC3H18, functions as a nuclear transcriptional activator and enhances abiotic stress tolerance in sweet potato.

CCCH-type zinc-finger proteins play essential roles in regulating plant development and stress responses. However, the molecular and functional properties of non-tandem CCCH-type zinc-finger (non-TZF) proteins have been rarely characterized in plants. Here, we report the biological and molecular characterization of a sweet potato non-TZF gene, IbC3H18. We show that IbC3H18 exhibits tissue- and abiotic stress-specific expression, and could be effectively induced by abiotic stresses, including NaCl, polyethylene glycol (PEG) 6000, H2 O2 and abscisic acid (ABA) in sweet potato. Accordingly, overexpression of IbC3H18 led to increased, whereas knock-down of IbC3H18 resulted in decreased tolerance of sweet potato to salt, drought and oxidation stresses. In addition, IbC3H18 functions as a nuclear transcriptional activator and regulates the expression of a range of abiotic stress-responsive genes involved in reactive oxygen species (ROS) scavenging, ABA signaling, photosynthesis and ion transport pathways. Moreover, our data demonstrate that IbC3H18 physically interacts with IbPR5, and that overexpression of IbPR5 enhances salt and drought tolerance in transgenic tobacco plants. Collectively, our data indicate that IbC3H18 functions in enhancing abiotic stress tolerance in sweet potato, which may serve as a candidate gene for use in improving abiotic stress resistance in crops.

Reduced TIPE2 expression is inversely associated with proinflammatory cytokines and positively correlated with bone mineral density in patients with osteoporosis.

AIMS: The tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) participates in multiple inflammatory diseases. However, its underlying mechanism in osteoporosis has not been elucidated. The aim of current study is to preliminarily clarify the function of TIPE2 in the pathogenesis of osteoporosis. MAIN METHODS: TIPE2 expression in patients with osteoporosis was measured by Western blot and qRT-PCR methods. Proinflammatory cytokines including TNF-α, IL-1 and IL-6 were assessed via enzyme-linked immunosorbent assay. Serum fasting PINP and ß-CTX were measured by the chemiluminescence method. Simple logistic regression analysis was performed for the odds ratio (OR) for TIPE2. KEY FINDINGS: TIPE2 expression in patients with osteoporosis was dramatically decreased and negatively correlated with proinflammatory cytokines. Furthermore, TIPE2 level was negatively correlated with fasting ß-CTX, but not PINP, indicating that TIPE2 participates in the pathogenesis of osteoporosis dominantly by supression of bone resorption. Interestingly, TIPE2 expression level was positively correlated with bone mineral density (BMD), and its expression level can predict the risk of bone fracture using the simple logistic regression assay. SIGNIFICANCE: Our findings clarify that TIPE2 alleviates the pathogenesis of osteoporosis by suppressing the inflammatory status and the ability of TIPE2 for predicts bone fracture further demonstrated that TIPE2 might serve as a novel diagnostic marker and a therapeutic target for osteoporosis.

TIPE2 sensitizes osteosarcoma cells to cis-platin by down-regulating MDR1 via the TAK1- NF-κB and - AP-1 pathways.

TIPE2 participates in multiple types of cancer development. However, its mechanism underlying chemoresistance in osteosarcoma has not been elucidated. Herein, we observed the expression of TIPE2 and MDR1 in cis-platin-resistant osteosarcoma tissues and cell lines. Compared to their matched sensitive cell lines and tissues, TIPE2 was downregulated while MDR1 expression was increased. Further investigation showed that overexpression of TIPE2 effectively inhibited MDR1 expression and greatly sensitized osteosarcoma cells to cis-platin, both in vivo and in vitro. Mechanistically, TIPE2 inhibited the transcription of the MDR1 promoter by interfering with the TAK1-NF-κB and -AP-1 pathways. Overall, our results elucidated for the first time that TIPE2 sensitizes osteosarcoma cells to cis-platin through downregulation of MDR1 and may be a novel target in osteosarcoma therapy.

Arabidopsis small ubiquitin-related modifier protease ASP1 positively regulates abscisic acid signaling during early seedling development.

The small ubiquitin-related modifier (SUMO) modification plays an important role in the regulation of abscisic acid (ABA) signaling, but the function of the SUMO protease, in ABA signaling, remains largely unknown. Here, we show that the SUMO protease, ASP1 positively regulates ABA signaling. Mutations in ASP1 resulted in an ABA-insensitive phenotype, during early seedling development. Wild-type ASP1 successfully rescued, whereas an ASP1 mutant (C577S), defective in SUMO protease activity, failed to rescue, the ABA-insensitive phenotype of asp1-1. Expression of ABI5 and MYB30 target genes was attenuated in asp1-1 and our genetic analyses revealed that ASP1 may function upstream of ABI5 and MYB30. Interestingly, ASP1 accumulated upon ABA treatment, and ABA-induced accumulation of ABI5 (a positive regulator of ABA signaling) was abolished, whereas ABA-induced accumulation of MYB30 (a negative regulator of ABA signaling) was increased in asp1-1. These findings support the hypothesis that increased levels of ASP1, upon ABA treatment, tilt the balance between ABI5 and MYB30 towards ABI5-mediated ABA signaling.

Efficacy of Compounds Isolated from the Essential Oil of Artemisia lavandulaefolia in Control of the Cigarette Beetle, Lasioderma serricorne.

To develop natural product resources to control cigarette beetles (Lasioderma serricorne), the essential oil from Artemisia lavandulaefolia (Compositae) was investigated. Oil was extracted by hydrodistillation of the above-ground portion of A. lavandulaefolia and analyzed using gas chromatography-mass spectrometer (GC-MS). Extracted essential oil and three compounds isolated from the oil were then evaluated in laboratory assays to determine the fumigant, contact, and repellent efficacy against the stored-products' pest, L. serricorne. The bioactive constituents from the oil extracts were identified as chamazulene (40.4%), 1,8-cineole (16.0%), and ß-caryophyllene (11.5%). In the insecticidal activity assay, the adults of L. serricorne were susceptible to fumigant action of the essential oil and 1,8-cineole, with LC50 values of 31.81 and 5.18 mg/L air. The essential oil, 1,8-cineole, chamazulene, and ß-caryophyllene exhibited contact toxicity with LD50 values of 13.51, 15.58, 15.18 and 35.52 µg/adult, respectively. During the repellency test, the essential oil and chamazulene had repellency approximating the positive control. The results indicated that chamazulene was abundant in A. lavandulaefolia essential oil and was toxic to cigarette beetles.

Inhibition of REDD1 Sensitizes Bladder Urothelial Carcinoma to Paclitaxel by Inhibiting Autophagy.

Purpose: Regulated in development and DNA damage response-1 (REDD1) is a stress-related protein and is involved in the progression of cancer. The role and regulatory mechanism of REDD1 in bladder urothelial carcinoma (BUC), however, is yet unidentified.Experimental Design: The expression of REDD1 in BUC was detected by Western blot analysis and immunohistochemistry (IHC). The correlation between REDD1 expression and clinical features in patients with BUC were assessed. The effects of REDD1 on cellular proliferation, apoptosis, autophagy, and paclitaxel sensitivity were determined both in vitro and in vivo Then the targeted-regulating mechanism of REDD1 by miRNAs was explored.Results: Here the significant increase of REDD1 expression is detected in BUC tissue, and REDD1 is first reported as an independent prognostic factor in patients with BUC. Silencing REDD1 expression in T24 and EJ cells decreased cell proliferation, increased apoptosis, and decreased autophagy, whereas the ectopic expression of REDD1 in RT4 and BIU87 cells had the opposite effect. In addition, the REDD1-mediated proliferation, apoptosis, and autophagy are found to be negatively regulated by miR-22 in vitro, which intensify the paclitaxel sensitivity via inhibition of the well-acknowledged REDD1-EEF2K-autophagy axis. AKT/mTOR signaling initially activated or inhibited in response to silencing or enhancing REDD1 expression and then recovered rapidly. Finally, the inhibited REDD1 expression by either RNAi or miR-22 sensitizes BUC tumor cells to paclitaxel in a subcutaneous transplant carcinoma model in vivoConclusions: REDD1 is confirmed as an oncogene in BUC, and antagonizing REDD1 could be a potential therapeutic strategy to sensitize BUC cells to paclitaxel. Clin Cancer Res; 24(2); 445-59. ©2017 AACR.