Curcumin nanoparticles and the therapeutic potential of curcumin for musculoskeletal disorders.

Musculoskeletal disorders (MSD) are a collection of degenerative conditions impacting the body's bones, joints, muscles, tendons, ligaments, and nerves. MSDs affect approximately 1.71 billion individuals worldwide and are a significant cause of disability. Curcumin is a polyphenolic compound with anti-inflammatory, antioxidant, and antitumor properties. In this review, we will discuss the research progress of structural analogs, derivatives, and nanomaterials that can improve the bioavailability of this natural drug. Curcumin may potentially retard the progression of osteoporosis, osteoarthritis, and rheumatoid arthritis. These effects may be related to curcumin's targeting of multiple signalling pathways.

Application of fracture body surface localization film combined with CT volume rendering in the minimally invasive rib fractures internal fixation.

OBJECTIVE: To investigate the application value of the technique of fracture body surface localization film combined with CT volume rendering in the selection of minimally invasive incision for internal fixation of rib fractures. PATIENTS AND METHODS: Clinical data of 55 cases of patients who underwent internal fixation for rib fracture in our hospital from June 2019 to April 2020 were selected. The differences in the accuracy of preset incision, incision length, operation time, intraoperative blood loss, postoperative wound drainage, and postoperative pain score between the group with fracture body surface localization film combined with CT volume rendering (n=32) and the group with traditional localization method (n=23). RESULTS: Compared with traditional localization method, fracture body surface localization film combined with CT volume rendering could improve the accuracy of surgical incision, reduce the operation time, incision length, intraoperative blood loss, postoperative wound drainage, and postoperative pain score (p<0.05). CONCLUSIONS: The application of fracture body surface localization film combined with CT volume rendering has obvious effects on the accurate selection of incision of rib fracture internal fixation, and it is an effective method that is worthy of promotion.

Combination of biomechanical evaluation and accurate placement of dental implants: a new concept of virtual surgery in maxillary and mandibular functional reconstruction.

Biomechanics are crucial for bony regeneration and survival of implants in functional maxillary and mandibular reconstructions. However, we know of no study that has included an analysis of biomechanics to guide the optimal position of a fibular graft in virtual surgery. This study was designed to evaluate the combination of biomechanics and accurate placement of implants for virtual surgery in reconstruction of the jaw using fibular grafts. Thirty-one patients had maxillary or mandibular reconstruction with vascularised fibular grafts and the immediate placement of dental implants. Virtual studies were made preoperatively to evaluate the biomechanics and to assess the position of the fibular grafts with minimal distribution of stress. All operations proceeded accurately and with no complications with a mean (range) of 14 (6-20) months' follow-up. According to the individual biomechanical evaluations, the optimal position for the fibular graft is probably the middle of the mandibular body or below the bottom of the maxillary sinus. The combination of biomechanical evaluation and accurate placement of dental implants is a new concept that could achieve good biomechanical positioning of fibular grafts in the jaw and a desirable level of accuracy for functional reconstruction.

Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients.

OBJECTIVE: The ubiquitin-conjugating enzyme E2C (UBE2C) has been known as a crucial factor upregulated in various tumors. The functions of UBE2C is mainly involved in the pathway protein ubiquitination. This study investigates the expression of UBE2C in gastric cancers and its correlation with overall survival rate. MATERIALS AND METHODS: Real-time PCR (RT-PCR) and Western blotting were performed to determine the expression of UBE2C in gastric cancer samples and adjacent normal tissues. Immunohistochemical staining was used to assess the expression of UBE2C in 216 paraffin-embedded gastric cancer tissues. RESULTS: The mRNA and relevant protein levels of UBE2C in gastric cancer tissues are significantly greater than those in the adjacent normal tissues. Also, the expression of UBE2C is found to correlate with lymphatic metastasis, serosa invasion, TNM (Malignant Tumors) staging and Lauren's classification (p<0.05). The univariate analysis shows that the overexpression of UBE2C associates with poor prognosis (p=0.001). The multivariate analysis demonstrates that expression of UBE2C, lymphatic metastasis, and TNM staging are independent prognostic indicators. CONCLUSIONS: This study shows that overexpression of UBE2C contributes to the development of gastric cancer, and UBE2C has the potential to be exploited as a therapeutic target.

SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue squamous cell carcinoma by acting on the Wnt/ß-catenin pathway.

A sub-population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumor relapse and metastasis. In our study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin-resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin-resistant TSCC cells, which displayed CSC-like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumor stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin-resistant TSCC cells inhibited chemoresistance, tumorsphere formation, and EMT. The Wnt/ß-catenin pathway mediated the cancer stem-like properties in cisplatin-resistant TSCC cells. Further studies showed that the transfection of active ß-catenin in SOX8 stable-knockdown cells partly rescued the SOX8 silencing-induced repression of stem-like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled-7 (FZD7) and induced the FZD7-mediated activation of the Wnt/ß-catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7-mediated Wnt/ß-catenin pathway.

Long non-coding RNA TUSC7 expression is independently predictive of outcome in glioma.

OBJECTIVE: Down-regulation of long non-coding RNA tumor suppressor candidate 7(TUSC7) contributes to tumorigenesis in several human cancers including glioma. However, the prognostic value of TUSC7 in glioma remains unclear. The present study aimed to investigate the clinicopathological and prognostic value of TUSC7. PATIENTS AND METHODS: The expression level of TUSC7 in glioma tissues and matched normal tissues were detected by qRT-PCR. Then, the association of serum TUSC7 expression level with various important clinicopathological parameters and survival rates was evaluated. The Cox regression analysis was used to evaluate the effect of independent prognostic factors on survival outcome. RESULTS: The relative level of TUSC7 was significantly lower in glioma tissues compared to the adjacent normal brain tissues (p < 0.01). In addition, a lower expression of TUSC7 was observed in high-grade glioma tissues than in low-grade glioma tissues (p < 0.01). Furthermore, the low expression of TUSC7 was associated with poor clinicopathological characteristics of glioma, including WHO grade (p = 0.002) and KPS (p = 0.026). Then, the low TUSC7 level was correlated with shorter disease free survival (DFS) and overall survival (OS) than low level (both p = 0.05). Finally, univariate and multivariate Cox analysis showed that TUSC7 was an independent prognostic indicator for OS and DFS. CONCLUSIONS: These results provided evidence that TUSC7 may be a potential biomarker in the prognosis of glioma.

Triglyceride to high-density lipoprotein cholesterol ratio predicts worse outcomes after acute ischaemic stroke.

BACKGROUND AND PURPOSE: The effect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months. METHODS: Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were defined according to the modified Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0-1; good outcome, mRS 0-2; and death, mRS 6). RESULTS: In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; specificity 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; specificity 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; specificity 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% confidence interval 1.89-4.55) compared with patients with a TG/HDL-C ≥ 0.87. CONCLUSIONS: A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS.

STMN1 in colon cancer: expression and prognosis in Chinese patients.

OBJECTIVE: To study the stathmin (STMN1) expression in colorectal cancer and tumor-adjacent normal tissue and discuss its prognostic significance in colon cancer. PATIENTS AND METHODS: STMN1 was tested with qRT-PCR in 30 samples of fresh colon cancer tissue and tumor-adjacent issue, and with immunohistochemical SP method in 105 samples of fresh colon cancer tissue and tumor-adjacent issue to analyze the association between its expression and clinical pathological parameters. Clinical data was combined to study the relationship between STMN1 expression and 5-year survival rate. Univariate analysis and Cox multivariate regression were performed to study the correlation between STMN1 expression and prognosis. RESULTS: The mRNA and protein level of STMN1 were significantly higher in colon cancer samples than tumor-adjacent normal tissues (p<0.05). STMN1 expression was independent of patient age, gender or location, but significantly related to lymph node metastasis and TNM staging (p<0.05). Survival analysis by Kaplan-Meier method showed that STMN1 expression was significantly related with the survival of colon cancer patients. The median survival time of STMN1-positive patients (37.5 months) was significantly shorter than STMN1-negative patients (57.1 months, p<0.05). Cox multivariate regression indicated that STMN1 is independent prognostic factors predicting the development, invasion and metastasis of colon cancer (p<0.05). CONCLUSIONS: STMN1 overexpression in colon cancer is independently associated with improved survival and significantly related to the development of the disease. Our findings suggest that presence of a STMN1-prognosis interaction that potentially determines clinical outcome.

Expression level of NSE, S100B and NPY in children with acute miliary phthisis and secondary tubercular meningitis.

OBJECTIVE: To explore the expression level of neuron-specific enolase (NSE), S100B and neuropeptide Y (NPY) in children with acute miliary tuberculosis and secondary tubercular meningitis. PATIENTS AND METHODS: 28 children diagnosed with acute miliary tuberculosis and secondary tubercular meningitis were included into group A, 25 children diagnosed with pure acute miliary tuberculosis were included into group B and 23 children diagnosed with suspected meningitis were included into group C. The levels of NSE, S100B and NPY in cerebrospinal fluid and serum were detected. RESULTS: The levels of NSE, S100B and NPY in cerebrospinal fluid and serum of group A were significantly higher than the levels in the other two groups, differences were statistically significant (p<0.05). A multifactor retrospective analysis suggested that secondary tubercular meningitis was significantly correlated with the high expression of S100B, NPY and NSE in cerebrospinal fluid and serum. CONCLUSIONS: Early detection of the expression levels of NSE, S100B and NPY in cerebrospinal fluid and serum was of great value for the diagnosis of tubercular meningitis secondary to acute miliary tuberculosis.

High levels of phosphatase and tensin homolog expression predict favorable prognosis in patients with non-small cell lung cancer.

OBJECTIVE: The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. PATIENTS AND METHODS: In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. RESULTS: NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 versus 12.9 months, log-rank p = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 versus 15.54 months, log-rank p = 0.043). High levels of PTEN expression resulted in 43% reduction in risk for all NSCLC patients (HR = 0.57, 95% CI: 0.33-0.98, p = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex and tumor type (HR = 0.56, 95% CI: 0.32-0.99; p = 0.048; HR = 0.54, 95% CI: 0.36-0.97; p = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (p > 0.17). When levels of PTEN expression were binarized using the optimal cutpoint, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80% and 58% respectively, p = 0.049) and in patients with AC than in those with squamous-cell carcinoma (SCC) (78% and 58% respectively, p = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (p > 0.28). CONCLUSIONS: Our results suggest that high levels of PTEN expression may be favorable prognostic marker in NSCLC patients.

P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells.

BACKGROUND: Our previous study demonstrated that extracellular adenosine 5'-triphosphate (ATP) stimulated prostate cancer cell invasion via P2Y receptors. However, the purinergic receptor subtype(s) involved in this process remains unclear. Here we aimed to determine whether P2Y2, one subtype of P2Y receptors, was involved in the invasion and metastasis of prostate cancer cells, and elucidated the underlying mechanism. METHODS: RNAi was introduced to silence the expression of P2Y2. In vitro invasion and migration assays and in vivo experiments were carried out to examine the role of P2Y2 receptor in cell invasion and metastasis. cDNA microarray was performed to identify the differentially expressed genes downstream of ATP treatment. RESULTS: P2Y2 was significantly expressed in the prostate cancer cells. Knockdown of P2Y2 receptor suppressed cell invasion and metastasis in vitro and in vivo. Further experiments identified that ATP could promote IL-8 and Snail expression and inhibit E-cadherin and Claudin-1 expression. Knockdown of P2Y2 receptor affected the expression of these EMT/invasion-related genes in vitro and in vivo. CONCLUSION: P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells via some EMT/invasion-related genes. Thereby, P2Y2 receptor could be a potential therapeutic target for the treatment of prostate cancer.

Tailoring of keV-ion beams by image charge when transmitting through rhombic and rectangular shaped nanocapillaries.

We report on an unexpected effect of tailoring transmission profiles of Ne(7+) ions through nanocapillaries of rhombic and rectangular cross sections in mica. We find that capillaries of rhombic cross sections produce rectangular shaped ion transmission profiles and, vice versa, that capillaries of rectangular geometry give a rhombic beam shape. This shaping effect only occurs for transmitted ions and is absent for the small fraction of neutralized particles. The experimental findings and simulations of the projectile trajectories give clear evidence that the observed effect is due to the image forces experienced by the transmitting ions. This novel beam shaping mechanism suggests applications for the guiding, focusing, and shaping of ion beams.

A novel DNA extraction and duplex polymerase chain reaction assay for the rapid detection of Prototheca zopfii genotype 2 in milk.

AIMS: To develop a PCR-based assay to detect Prototheca zopfii (P. zopfii) and its mastitis-related subtype (genotype 2) directly from milk samples. METHODS AND RESULTS: The DNA extraction method herein is based on the lysing properties of chemical agents, mechanical grinding and DNA-binding properties of silica particles; this method was developed to rapidly extract DNA directly from P. zopfii in bovine milk. Two pairs of primers specific for P. zopfii and genotype 2 were used in the duplex PCR, and a sensitivity test showed that the detection level was 5 × 10(2) colony-forming units (CFU) ml(-1) for P. zopfii and 5 × 10(3) CFU ml(-1) for genotype 2. Furthermore, a practical survey of 23 milk samples showed that the assay produced results that were in accordance with those obtained by the conventional microbiology method. CONCLUSIONS: The DNA extraction method is effective in isolating sufficient quantities of DNA from P. zopfii in milk for PCR analysis. The PCR assay is economical, sensitive and more rapid than the conventional culture method. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay could be used as an alternative method for the rapid the detection of bovine mastitis resulting from P. zopfii genotype 2.

Activation of extracellular signal-regulated protein kinase is associated with colorectal distension-induced spinal and supraspinal neuronal response and neonatal maternal separation-induced visceral hyperalgesia in rats.

The activation of extracellular signal-regulated protein kinase (ERK) is essential for pain sensation and development of hyperalgesia in chronic pathological pain. Neonatal maternal separation (NMS) could trigger behavioral hyperalgesia and upregulate central neuronal activity in rats. The present study aims to investigate whether ERK associates with the colorectal distension (CRD)-evoked neuronal response and the upregulated central sensitivity to CRD in NMS rats. Male Sprague-Dawley rat pups were either subjected to NMS or not handled (NH) from postnatal day 2 to day 14. The protein expression of phospho-ERK (p-ERK) and c-fos at the spinal and supraspinal levels of adult rats were quantified and their correlation was analyzed. Western blot analysis revealed significant NMS effect on p-ERK expression in the lumbosacral dorsal horn and thalamus. Immunohistochemistry analysis demonstrated that CRD elevated p-ERK and c-fos expression in the dorsal root ganglia (DRG), laminae I-II of the lumbosacral dorsal horn, thalamic nucleus central medial (CM), paraventricular thalamic nucleus (PV), and anterior cingulate cortex (ACC). Significant NMS effect on p-ERK and c-fos expression was observed in the DRG, and laminae I-II, III-IV, and X of the lumbosacral dorsal horn. Furthermore, a significant interactive effect of NMS and CRD on p-ERK expression was observed in laminae III-IV of the lumbosacral dorsal horn. Correlation analysis revealed the positive association between c-fos- and p-ERK-immunoreactive nuclei numbers in the DRG, lumbosacral dorsal horn, and ACC. These results demonstrate that ERK is actively involved in CRD-evoked neuronal activation in both NH and NMS rats. Moreover, ERK is associated with the upregulated central neuronal sensitivity to noxious CRD in NMS rats, which may be responsible for the behavioral hyperalgesia in NMS rat.

Evidence of sequentially formed charge patches guiding ions through nanocapillaries.

We investigated the time evolution of the dynamically shifting distribution of 7 keV Ne7+ ions guided through nanocapillaries in SiO2. We present evidence for a small number of charge patches, formed sequentially in the charging-up process, guiding the ions. We show that the charge patches are distributed along the whole length of the capillaries and that they are maintained in the equilibrium state of transmission. The interpretations are supported by model calculations.

Phylogeny of Hystrix and related genera (Poaceae: Triticeae) based on nuclear rDNA ITS sequences.

The taxonomic status of Hystrix and phylogenetic relationships among Hystrix and its related genera of Pseudoroegneria (St), Hordeum (H), Psathyrostachys (Ns), Elymus (StH), Leymus (NsXm), Thinopyrum bessarabicum (E(b)) and Lophopyrum elongatum (E(e)) were estimated from sequences of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. The type species of Hystrix, H. patula, clustered with species of Pseudoroegneria, Hordeum, Elymus, Th. bessarabicum and Lo. elongatum, while H. duthiei ssp. duthiei, H. duthiei ssp. longearistata, H. coreana and H. komarovii were grouped with Psathyrostachys and Leymus species. The results indicate that: (i) H. patula is distantly related to other species of Hystrix, but is closely related to Elymus species; (ii) H. duthiei ssp. duthiei, H. duthiei ssp. longearistata, H. coreana and H. komarovii have a close affinity with Psathyrostachys and Leymus species, and H. komarovii might contain the NsXm genome of Leymus; and (iii) the St, H and Ns genomes in Hystrix originate from Pseudoroegneria, Hordeum and Psathyrostachys, respectively, while the Xm in Hystrix and Leymus has a complex relationship with the E or St genomes. According to the genomic system of classification in Tiritceae, it is reasonable to treat Hystrix patula as Elymus hystrix L, and the other species of Hystrix as species of a section of Leymus, Leymus Sect. Hystrix.

Identification of a new HLA-B*56 variant, B*5614.

In this report, the novel allele B*5614 is presented. The allele was identified in a Chinese individual by sequence-based typing. HLA-B*5614 differs from B*5608 by a single nucleotide at position 277G-->C in exon 2. This results in an amino acid change from Gly to Arg at codon 93.

Identification of HLA-B*5136 in the Chinese population.

We report here a new HLA-B*5136 allele identified by sequence-based typing in the Chinese population. The new B*5136 allele showed four nucleotides difference with B*5108 at exon 3, which are two point mutations at nucleotide positions 527 T-->A and 583 C-->T, and two substitutions at adjacent nucleotide positions 559 C-->A and 560 T-->C. This results in three amino acid changes from Val to Glu at codon 177, Leu to Thr at codon 187, and His to Tyr at codon 195.