Preparation, in vitro anti-tumour activity and in vivo pharmacokinetics of RGD-decorated liposomes loaded with shikonin.

Shikonin (SHK) has been evidenced to possess effects against various cancer cells. However, poor aqueous solubility and high toxicity restrict its application. In the study, RGD-decorated liposomes loaded with SHK (RGD-Lipo-SHK) were prepared via thin-film hydration method. Characterization and cellular uptake of liposomes was evaluated. Cytotoxicity of blank liposomes and different SHK formulations was measured against breast cancer cells (MDA-MB-231, MCF-7, and MCF-10A). Anti-tumour effects and pharmacokinetic parameters of different SHK formulations were appraised in tumour spheroids and in rat model, respectively. Liposomes displayed a particle size of less than 127 nm with a polydispersity index about 0.21. The encapsulation efficiency was about 91% for SHK, and drug leakage rate of liposomes was less than 6%. RGD-Lipo-SHK showed superior cellular internalization in the αvß3-positive MDA-MB-231 cells. Blank liposomes had no cytotoxicity to MDA-MB-231 and MCF-7 cells. Howbeit, different SHK formulations obviously inhibited proliferation of MCF-10A cells, especially free SHK. Meanwhile, RGD-Lipo-SHK significantly inhibited growth inhibition of tumour spheroids. The pharmacokinetics study indicated that the peak concentration, area under plasma concentration-time curves, half-life, and mean residence time of RGD-Lipo-SHK distinctly increased compared with those of free SHK. Altogether, these results demonstrated RGD-Lipo-SHK could reduce cytotoxicity, strengthen the antitumor-targeted effect, and prolong circulation time, which provides a foundation for further in vivo experimentations.

Protein kinase CK2: An emerging regulator of cellular metabolism.

The protein kinase casein kinase 2 (CK2) exerts its influence on the metabolism of three major cellular substances by phosphorylating essential protein molecules involved in various cellular metabolic pathways. These substances include hormones, especially insulin, rate-limiting enzymes, transcription factors of key genes, and cytokines. This regulatory role of CK2 is closely tied to important cellular processes such as cell proliferation and apoptosis. Additionally, tumor cells undergo metabolic reprogramming characterized by aerobic glycolysis, accelerated lipid ß-oxidation, and abnormally active glutamine metabolism. In this context, CK2, which is overexpressed in various tumors, also plays a pivotal role. Hence, this review aims to summarize the regulatory mechanisms of CK2 in diverse metabolic pathways and tumor development, providing novel insights for the diagnosis, treatment, and prognosis of metabolism-related diseases and cancers.

Possible Mechanisms of Dark Tea in Cancer Prevention and Management: A Comprehensive Review.

Tea is one of the most popular drinks in the world. Dark tea is a kind of post-fermented tea with unique sensory characteristics that is produced by the special fermentation of microorganisms. It contains many bioactive substances, such as tea polyphenols, theabrownin, tea polysaccharides, etc., which have been reported to be beneficial to human health. This paper reviewed the latest research on dark tea's potential in preventing and managing cancer, and the mechanisms mainly involved anti-oxidation, anti-inflammation, inhibiting cancer cell proliferation, inducing cancer cell apoptosis, inhibiting tumor metastasis, and regulating intestinal flora. The purpose of this review is to accumulate evidence on the anti-cancer effects of dark tea, the corresponding mechanisms and limitations of dark tea for cancer prevention and management, the future prospects, and demanding questions about dark tea's possible contributions as an anti-cancer adjuvant.

Targeting diacylglycerol kinase α impairs lung tumorigenesis by inhibiting cyclin D3.

BACKGROUND: Diacylglycerol kinase α (DGKA) is the first member discovered from the diacylglycerol kinase family, and it has been linked to the progression of various types of tumors. However, it is unclear whether DGKA is linked to the development of lung cancer. METHODS: We investigated the levels of DGKA in the lung cancer tissues. Cell growth assay, colony formation assay and EdU assay were used to examine the effects of DGKA-targeted siRNAs/shRNAs/drugs on the proliferation of lung cancer cells in vitro. Xenograft mouse model was used to investigate the role of DGKA inhibitor ritanserin on the proliferation of lung cancer cells in vivo. The downstream target of DGKA in lung tumorigenesis was identified by RNA sequencing. RESULTS: DGKA is upregulated in the lung cancer cells. Functional assays and xenograft mouse model indicated that the proliferation ability of lung cancer cells was impaired after inhibiting DGKA. And cyclin D3(CCND3) is the downstream target of DGKA promoting lung cancer. CONCLUSIONS: Our study demonstrated that DGKA promotes lung tumorigenesis by regulating the CCND3 expression and hence it can be considered as a potential molecular biomarker to evaluate the prognosis of lung cancer patients. What's more, we also demonstrated the efficacy of ritanserin as a promising new medication for treating lung cancer.

Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury.

BACKGROUND: Radiation-induced lung injury (RILI) is the most common and serious complication of chest radiotherapy. However, reported radioprotective agents usually lead to radiation resistance in tumor cells. The key to solving this problem is to distinguish between the response of tumor cells and normal lung epithelial cells to radiation damage. METHODS: RNA-Seq was used to recognize potential target of alleviating the progression of RILI as well as inhibiting tumor growth. The activation of NLRP3 inflammasome in lung epithelial cells was screened by qRT-PCR, western blotting, immunofluorescence, and ELISA. An in vivo model of RILI and in vitro conditioned culture model were constructed to evaluate the effect of NLRP3/interleukin-1ß on fibroblasts activation. ROS, ATP, and (NADP)+/NADP(H) level in lung epithelial cells was detected to explore the mechanism of NLRP3 inflammasome activation. The lung macrophages of the mice were deleted to evaluate the role of lung epithelial cells in RILI. Moreover, primary cells were extracted to validate the results obtained from cell lines. RESULTS: NLRP3 activation in epithelial cells after radiation depends on glycolysis-related reactive oxygen species accumulation. DPYSL4 is activated and acts as a negative regulator of this process. The NLRP3 inflammasome triggers interleukin-1ß secretion, which directly affects fibroblast activation, proliferation, and migration, eventually leading to lung fibrosis. CONCLUSIONS: Our study suggests that NLRP3 inflammasome activation in lung epithelial cells is essential for radiation-induced lung injury. These data strongly indicate that targeting NLRP3 may be effective in reducing radiation-induced lung injury in clinical settings.

Emerging role of Protein Kinase CK2 in Tumor immunity.

Protein kinase CK2, a conserved serine/threonine-protein kinase, is ubiquitous in cells and regulates various intracellular processes, especially in tumor cells. As one of the earliest discovered protein kinases in humans, CK2 plays a crucial role in phosphorylating or associating with hundreds of substrates to modulate several signaling pathways. Excellent reviews have reported that the overexpression of CK2 could be observed in many cancers and was closely associated with tumor occurrence and development. The elevation of CK2 is also an indicator of a poor prognosis. Recently, increasing attention has been paid to the relationship between CK2 and tumor immunity. However, there is no comprehensive description of how CK2 regulates the immune cells in the tumor microenvironment (TME). Also, the underlying mechanisms are still not very clear. In this review, we systematically summarized the correlation between CK2 and tumor immunity, primarily the effects on various immune cells, both in innate and adaptive immunity in the TME. With the comprehensive development of immunotherapy and the mounting transformation research of CK2 inhibitors from the bench to the clinic, this review will provide vital information to find new treatment options for enhancing the efficacy of immunotherapy.

Using the lamina nutrient foramen as the entry point for posterior cervical pedicle screw placement.

STUDY DESIGN: A prospective study and technique description. OBJECTIVE: This study introduced a method for posterior cervical pedicle screw placement by using the bilateral posterior lamina nutrient foramens as the entry point. METHODS: Firstly, 30 dry C3-C7 vertebrae specimens were harvested for measurement. The lamina nutrient foramens were used as the entry points for posterior cervical pedicle screw placement and four linear and two angle parameters were obtained from a computed tomography scan(CT). Then, 60 patients who underwent C3-C7 pedicle screw fixation using this method were included, linear and angle parameters were obtained from a postoperative CT. RESULTS: The average incidences of lamina nutrient foramen on the C3-C7 specimens were 88.3%, 90.0%, 95.0%, 95.0%, and 96.7%, respectively. The distances from the entry point to the pedicle screw tip (OD), the pedicle transverse angles (α), and the pedicle sagittal angles (ß) measure for the entry points from C3-C7 were 28.74 ± 3.45-30.15 ± 2.01 mm, 26.88 ± 6.89° to 32.72 ± 5.91°, and 12.48 ± 9.31° to 19.71 ± 8.45°, respectively, with no significant differences between the left and right sides. In the 60 patients who underwent surgery, the lengths of the pedicle screws (PL) were 28.34 ± 2.25-30.15 ± 2.31 mm, the pedicle transverse angles (α) were 26.89 ± 6.86° to 32.36 ± 5.65°, and the pedicle sagittal angles (ß) were 12.49 ± 9.11° to 20.06 ± 8.91°. The new method had a 96.8% (454/469) success rate among these patients, with no screws penetrating the spinal canal or signs of vertebral artery injury. CONCLUSION: Entry at the bilateral lamina nutrient foramen represents an alternative posterior cervical pedicle screw placement technique that is feasible and safe.

Risk Factors for Surgical Site Infection After Posterior Lumbar Spinal Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study was to identify the independent risk factors for postoperative surgical site infection (SSI) after posterior lumbar spinal surgery based on the perioperative factors analysis. SUMMARY OF BACKGROUND DATA: SSI is one of the most common complications after spinal surgery. Previous studies have identified different risk factors for postoperative SSI after lumbar spinal surgery. However, most of the studies were focused on the patient and procedure-related factors. Few studies reported the correlation between laboratory tests and postoperative SSI. METHODS: A retrospective study was carried out in a single institution. Patients who underwent posterior lumbar spinal surgery between January 2010 and August 2016 were included in this study. All patients' medical records were reviewed and patients with postoperative SSI were identified. Perioperative variables were included to determine the risk factors for SSI by univariate and multivariate regression analysis. RESULTS: A total of 2715 patients undergoing posterior lumbar spinal surgery were included in this study. Of these patients, 64 (2.4%) were detected with postoperative SSI, including 46 men and 18 women. Diabetes mellitus (P = 0.026), low preoperative serum level of calcium (P = 0.009), low preoperative and postoperative albumin (P = 0.025 and 0.035), high preoperative serum glucose (P = 0.029), multiple fusion segments (P < 0.001), increased surgical time and estimated blood loss (P = 0.023 and 0.005), decreased postoperative hemoglobin (P = 0.008), and prolonged drainage duration (P = 0.016) were found to be the independent risk factors for SSI. Multilevel fusion and a history of diabetes mellitus were the two strongest risk factors (odds ratio = 2.329 and 2.227) for SSI. CONCLUSION: Based on a large population analysis, previous reported risk factors for SSI were confirmed in this study while some new independent risk factors were identified significantly associated with SSI following lumbar spinal surgery, including preoperative low serum level of calcium, decreased preoperative and postoperative albumin, and decreased postoperative hemoglobin. LEVEL OF EVIDENCE: 4.

Incidence and risk factors for symptomatic spinal epidural haematoma following lumbar spinal surgery.

PURPOSE: Spinal epidural haematoma (SEH) is a common complication after lumbar spinal decompression surgery, and symptomatic SEH usually causes devastating neurological deficits. Although different risk factors for post-operative SEH have been reported, few studies focused on patients' laboratory tests. The purpose of this study was to analyze the incidence of symptomatic SEH following lumbar spinal surgery, as well as identify the risk factors for it. METHODS: Patients who underwent posterior lumbar spinal decompression surgery between January 2010 and August 2016 were included in this study and their medical records were retrospectively reviewed. Those who developed post-operative symptomatic SEH after the surgery were identified. The risk factors for SEH were analyzed by univariate and multivariate regression analysis. RESULTS: In total, 2715 patients were included in this study and 31 (1.14%) were identified with post-operative symptomatic SEH. Of these patients, 19 were males and 12 were females, with an average age of 59.39 ± 11.66 years. After multivariate logistic regression analysis, low serum calcium level (P = 0.025), blood type A (P = 0.04), increased estimated blood loss (P = 0.032), prolonged surgical duration (P = 0.018), and decreased post-operative globulin (P = 0.016) were identified as the independent risk factors for post-operative SEH following lumbar spinal surgery. Furthermore, prolonged surgical duration (odds ratio = 3.105) was the strongest risk factor for SEH. CONCLUSION: Based on a large population investigation, the incidence of symptomatic SEH following lumbar spinal decompression surgery was 1.14%. Blood type A, increased estimated blood loss, and prolonged surgical duration were identified as the independent risk factors for post-operative SEH while two new risk factors, including low serum calcium level and decreased post-operative globulin, were firstly identified in this study.

Unplanned Reoperation of Lumbar Spinal Surgery During the Primary Admission: A Multicenter Study Based on a Large Patient Population.

STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study was to identify the rates and reasons, and the risk factors for unplanned reoperation of lumbar spinal surgery during the primary admission in terms of a multicenter and a large patient population study. SUMMARY OF BACKGROUND DATA: Unplanned reoperation is suggested to be a useful quality indicator for spinal surgery. However, the rates of unplanned reoperation in patients underwent lumbar spinal surgery during the primary admission are not well established. METHODS: This study was performed to review all the patients who underwent lumbar spinal surgery at three institutions from January 2010 to April 2015. Patients with unplanned reoperations after primary surgery during the same admission were included in this study. The demographics, diagnosis, surgical procedure, and complications of patients were reviewed and statistical analysis was performed to investigate the incidences and risk factors of unplanned revision. RESULTS: A total of 3936 patients who underwent lumbar spinal surgery from three institutions were reviewed, and 82 (2.08%) required unplanned reoperation during the primary admission because of wound infection (0.94%), screw misplacement (0.53%), cerebrospinal fluid leakage (0.27%), wound hematoma (0.18%), and neurologic deficit (0.15%). For the diagnosis, patients with lumbar spinal spondylolisthesis had a much higher rate of reoperation (4.3%) than those of lumbar stenosis (2.3%), vertebral tumor (2.2%), vertebral fracture (1.2%), and disc herniation (1.1%) with a significant difference (P < 0.001). The revision rate was significantly higher in patients underwent posterior lumbar interbody fusion than those received transforaminal lumbar interbody fusion (P = 0.007). CONCLUSION: Unplanned reoperation rate of lumbar spinal surgery was 2.08% and the most common reasons for it were wound infection and screw misplacement. Patients with a diagnosis of lumbar spinal spondylolisthesis or who underwent posterior lumbar interbody fusion were more likely to required unplanned reoperation during the primary admission. LEVEL OF EVIDENCE: 4.

A comparative study of perioperative complications between transforaminal versus posterior lumbar interbody fusion in degenerative lumbar spondylolisthesis.

BACKGROUND: Both posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) are accepted surgical techniques for the treatment of degenerative lumbar spondylolisthesis (DLS). However, it is still unclear one technique offers distinct advantages over the other. OBJECTIVE: A retrospective study was performed to compare perioperative complications and functional outcomes of patients undergoing TLIF versus PLIF for DLS. METHODS: A total of 226 consecutive patients who underwent surgery for treatment of DLS at three institutions were evaluated from January 2012 to December 2014. In this series, 125 patients underwent PLIF and 101 received TLIF. The operative time, blood loss, allogeneic blood transfusion rate and perioperative complications (including re-operative rate, nerve root injury, dural tear, wound infection) were compared between the two groups. Pain (VAS) and functional outcomes of patients (Kirkaldy-Willis criteria) were quantified before surgery and 1 week after surgery. RESULTS: Patients involved in the two groups had similar baseline demographic, clinical and radiographic characteristics. The PLIF group was associated with a higher incidence of post-operative iatrogenic nerve root dysfunction [12 cases (9.6 %) versus 2 cases (1.9 %), P = 0.018] and dural tears [15 cases (12 %) versus 4 cases (3.9 %), P = 0.030]. The re-operation rate was significantly higher in patients undergoing PLIF [13 cases (10.4 %) versus 2 cases (1.9 %), P = 0.011]. In addition, intra-operative blood loss, operative times, and allogeneic blood transfusion rates were higher in the PLIF group when compared to the TLIF group (P < 0.05). The wound infection rate of the PLIF group was similar to that of the TLIF group (7.2 versus 5.0 %, P = 0.486). VAS scores were decreased from 7.08 ± 1.13 to 2.84 ± 0.89 in the PLIF group, and from 7.18 ± 1.09 to 2.84 ± 0.91 in the TLIF group, respectively (P = 0.32). 85.6 % of patients in the TLIF group had good or excellent functional outcomes within the first post-operative week compared to 83.2 % in the PLIF group (P = 0.64). CONCLUSION: Both PLIF and TLIF were equally beneficial in improving short-term functional outcomes for patients with DLS. However, PLIFs were associated with statistically significant higher incidences of nerve root injury, dural tears, allogeneic blood transfusion, increased intra-operative times, blood loss and re-operations. Therefore, caution should be exercised when considering PLIFs.

[Comparison of serum specific IgE and skin prick test in allergic rhinitis patients sensitive to dust mite].

OBJECTIVE: To investigate the correlation of serum specific IgE and skin prick test in allergic rhinitis patients sensitive to dust mite and the difference between the results. METHOD: Data of 349 allergic rhinitis patients who had positive result in either Dermatophagoides pteronyssinus(Der p) or Dermatophagoides farinae (Der f) by serum specific IgE and skin prick test were statistically analyzed. RESULT: Grades of Skin prick test and specific IgE levels were notably relevant in these two dust mites(Der p r= 0. 568, Der f r= 0. 506, P<0. 01). There was significant difference of positive rates between serum specific IgE and skin prick test in Der p(Chi2 = 11. 605, P<0. 01)but not in Der f(Chi2 =0, P>0.05). There was no correlation between positive degree of two methods and score of clinical symptoms in allergic rhinitis. CONCLUSION: Serum specific IgE and skin prick test were notably relevant in allergic rhinitis patients sensitive to dust mites. The positive rates of the two methods were different due to different allergen. Therefore, they could not substitute for each other. The level of serum specific IgE and positive degree of skin prick test could not reflect the degree of symptom in allergic rhinitis.

[The effects of subcutaneous allergen immunotherapy by Alutard SQ allergy vaccination in management of perennial allergic rhinitis].

OBJECTIVE: To study the effects of subcutaneous allergen immunotherapy by Alutard SQ allergy vaccination in management of perennial allergic rhinitis. METHOD: Thirty-eight cases of the perennial allergic rhinitis received the subcutaneous allergen immunotherapy by Alutard SQ allergy vaccination for 3 years or more than 3 years. The clinical symptoms and signs were compared before and after treatment. RESULT: Good result were obtained in 21 of 38 cases, 7 cases effective, and 10 cases ineffective. Total effective rate was 73.68%. CONCLUSION: The subcutaneous allergen immunotherapy by Alutard SQ allergy vaccination was very effective for the perennial allergen rhinitis.