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Zhi-Gang Tan, Qian Zhou, Tao Huang, Yugang JiangDepartment of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaObjectives: Deep brain stimulation (DBS) is the surgical procedure for patients with advanced Parkinson’s disease. Globus pallidus internus (GPi) and subthalamic nucleus (STN) are the most targeted locations for the procedure. To investigate the variable efficiencies for the two different locations, we conducted a meta-analysis to compare both stimulation sites.Materials and methods: A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. Randomized controlled trials comparing the efficacies of GPi and STN DBS were included. Clinical outcomes of motor function, nonmotor function, and quality of life (QOL) were collected for the meta-analysis.Results: Ten eligible trials with 1,034 patients were included in the analysis. Unified Parkinson’s disease rating scale III (UPDRS-III) scores were collected at 6, 12, and 24 months postsurgery separately to assess the motor function of the patients. A statistically significant effect in favor of the GPi DBS was obtained in the off-medication/on-stimulation phase of UPDRS-III at 12 months (mean difference [MD] =6.87, 95% confidence interval [95% CI]: 3.00–10.74, P=0.57, I2=0%). However, GPi DBS showed an opposite result at 24 months (MD =−2.46, 95% CI: −4.91 to −0.02, P=0.05, I2=0%). In the on-medication/on-stimulation phase, GPi DBS obtained a worse outcome compared with STN DBS (MD =−2.90, 95% CI: −5.71 to −0.09, P=0.05, I2=0%). Compared with STN DBS, increased dosage of levodopa equivalent doses was needed in GPi DBS (standardized MD =0.60, 95% CI: 0.46–0.74, P

Objective: Epilepsy is a chronic brain disease with recurrent seizures. Autophagy plays a crucial role in the progression of epilepsy. This study aimed to explore the function and intrinsic mechanism of the long non-coding RNA (lncRNA) UCA1/miR-132-3p/ATG16L1 axis in epilepsy via regulation of autophagy., Methods: The expression of lncRNA UCA1, miR-132-3p and ATG16L1 was measured in serum from epileptic patients by quantitative RT-PCR. A SH-SY5Y cell model was further constructed using retinoic acid to investigate the UCA1/ miR-132-3p/ATG16L1 axis by quantitative RT-PCR, western blotting, fluorescence in situ hybridisation, RNA immunoprecipitation, chromatin immunoprecipitation, and a dual-luciferase reporter gene assay., Results: In the serum of epileptic patients, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated, compared to controls. Similarly, in the SH-SY5Y cell model, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated in retinoic acid-treated cells; lncRNA UCA1 was mainly located in the cytoplasm. lncRNA UCA1 overexpression was shown to promote autophagic gene expression, which was reversed by miR-132-3p overexpression. Moreover, autophagic gene expression induced by miR-132-3p knockdown was reversed by ATG16L1 knockdown. Based on precipitation assays, lncRNA UCA1 and miR-132-3p were shown to form a complex with the transcription factor, EZH2, and miR-132-3p was shown to interact with ATG16L1 based on a luciferase assay. Finally, lncRNA UCA1 was shown to negatively regulate miR-132-3p expression, and miR-132-3p was shown to negatively regulate ATG16L1., Significance: In this cell model, lncRNA UCA1 promotes autophagic gene expression via epigenetic regulation mediated by ATG16L1 and miR-132-3p.

To investigate the effect of long noncoding RNA (LINC01419)/miR-485-5p/LSM4 on the malignant behavior of hepatocellular carcinoma (HCC) cells. The expressions of LINC01419, miR-485-5p, and LSM4 were determined in HCC at the cellular and clinical levels, and cell biological behavior was evaluated. The relationships between LINC01419, miR-485-5p, and LSM4 were predicted and verified. Additionally, the subcellular localization of LINC01419 in HCC cells was analyzed. Finally, an animal experiment was conducted to confirm the effect of LINC01419 silencing on tumor growth. in HCC tissues and cells, LINC01419 and LSM4 were increasingly expressed, but miR-485-5p was decreasingly expressed. LINC01419 negatively regulated miR-485-5p- and miR-485-5p-targeted LSM4. LINC01419 was localized in the cytoplasm of HCC cells. Downregulation of miR-485-5p or upregulation of LSM4 reversed the inhibition of HCC cell malignant behavior by LINC01419 interference. LINC01419 sponges miR-485-5p to upregulate LSM4 expression, thereby facilitating the biological behavior of HCC cells., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objective: Copper-zinc superoxide dismutase (Cu-Zn SOD) is downregulated in epilepsy, however, the role of Cu-Zn SOD in epilepsy remains unclear., Methods: Based on the pilocarpine hydrochloride-induced rat model of epilepsy, cortical-striatum brain slices of rats were examined based on field excitatory post-synaptic potentials. Pathological changes were observed by transmission electron microscope. Also using SH-SY5Y cells, flow cytometry and TUNEL staining were applied to investigate cell apoptosis, and ELISA was applied to detect SOD activity. In addition, qRT-PCR and western blot were performed to detect SCN2A/Nrf2/HO-1 gene and protein expression levels, respectively., Results: Cu-Zn SOD over-expression suppressed epilepsy in vivo. In addition, Cu-Zn SOD knockdown notably decreased SOD activity and induced apoptosis in SH-SY5Y cells. Moreover, Cu-Zn SOD silencing decreased the levels of SCN2A, Nrf2 and HO-1. Lastly, Cu-Zn SOD was shown to modulate the NaV1.2/Nrf2/HO-1 axis in rats., Significance: In this model, Cu-Zn SOD attenuated epilepsy and was shown to alter the expression level of proteins of the NaV1.2 /Nrf2/HO-1 signalling pathway, indicating that Cu-Zn SOD might be a target for the treatment of epilepsy.

This study investigated possible therapeutic effect mechanisms of exosomes from bone marrow-derived mesenchymal stem cells (BMSC) in neuronal and microglial cells and in a Parkinson disease (PD) model. Neuronal SH-SY5Y cells and microglial HMC3 cells were subjected to 1-methyl-4-phenylpyridinium (MPP+) or LPS, respectively. The mRNA and protein expression was assessed using qRT-PCR, Western blotting, and enzyme-linked immunosorbent assay. Cell viability and apoptosis of SH-SY5Y cells were examined using the MTT assay and flow cytometry. Chromatin immunoprecipitation assays were performed to assess the binding relationship between glioma-associated oncogene homolog 1 (Gli1) and the Sp1 transcription factor promoter. BMSC-derived exosomes promoted cell proliferation and inhibited apoptosis in MPP+-treated SH-SY5Y cells and suppressed inflammatory markers in LPS-treated HMC3 cells. Sp1 knockdown decreased SH-SY5Y cell damage and HMC3 immune activation. Gli1 carried by BMSC exosomes directly bound with Sp1 to inhibit Sp1-mediated LRRK2 activation whereas exosomes secreted by Gli1-knockdown in BMSC did not. In a PD mouse model induced with MPTP, BMSC exosomes decreased neuron loss injury and the inflammatory response by inhibiting Sp1 signaling. Thus, BMSC-derived exosomal Gli1 alleviates inflammatory damage and neuronal apoptosis by inhibiting Sp1 in vitro and in vivo. These findings provide the basis for the potential clinical use of BMSC-derived exosomes in PD., (© 2022 American Association of Neuropathologists, Inc. All rights reserved.)

Background: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is an oncogenic lncRNA that has been reported in many cancers, but the role of SNHG3 in cholangiocarcinoma (CCA) remains largely unknown. Bioinformatic analysis revealed a regulatory relationship among SNHG3, miR-3173-5p, and ERG. miR-3173-5p is a tumour suppressive miRNA, while ERG is an oncogene. In the present study, we focused on the regulatory effects and molecular mechanisms of SNHG3 in CCA., Method: The expression of SNHG3 and miR-3173-5p was evaluated using qRT-PCR analysis. Knockdown of SNHG3 was achieved by shRNA. Cell viability was assessed by MTT assay. Migration and invasion were determined by Transwell assay. Flow cytometry was used to assess cell apoptosis. Western blots were applied to quantify protein levels. Furthermore, using RNA pulldown and dual luciferase assays, the interactions between SNHG3 and miR-3173-5p and between miR-3173-5p and ERG in CCA cells were validated., Results: SNHG3 was significantly upregulated in CCA cells compared with normal human intrahepatic biliary epithelial cells. Knockdown of SNHG3 inhibited the proliferation and migration of CCA cells. Mechanistically, SNHG3-sponged miR-3173-5p, thus releasing the repression of ERG by miR-3173-5p. Rescue experiments showed that the miR-3173-5p/ERG axis mediated the oncogenic effect of SNHG3., Conclusion: Taken together, our data suggest that SNHG3 is a pleiotropic oncogenic lncRNA in CCA. Knockdown of SNHG3 expression suppressed malignant phenotypes in CCA cells via the miR-3173-5p/ERG axis., (© 2021. The Society for Surgery of the Alimentary Tract.)

Based on the data mining technology, the rules of acupoint selection and prescription were analyzed for impotence treated with acupuncture and moxibustion in ancient recorded in Zhonghua Yidian . By taking " yangwei " and " yinwei " as the searching terms, the database of Zhonghua Yidian (the 5th edition) were retrieved and the relevant information of impotence, such as prescription provision, acupoints and use frequency were extracted. Using the software, e.g. Microsoft Excel and Weka 3.8.4, the rules of acupoint selection and prescription for impotence treated with acupuncture and moxibustion in ancient were analyzed. Fifty five provisions of acupoint prescriptions were in compliance with the requirements and screened. Of them, there were 17 compound prescriptions and the rest were the single-point prescriptions, with 24 acupoints involved. Regarding the use frequency of acupoints in treatment of impotence, the top 5 acupoints were Yingu (KI 10), Ququan (LR 8), Qichong (ST 30), Taichong (LR 3) and Rangu (KI 2). The cluster analysis found that Yingu (KI 10), Ququan (LR 8)-Qichong (ST 30), Taichong (LR 3)-Rangu (KI 2)-Xingjian (LR 2), and Mingmen (GV 4)-Zhongfeng (LR 4)-Yuji (LU 10)-Yanggu (SI 5) were formed the group prescriptions respectively. Multilayer correlation analysis discovered that the commonly used meridians were the liver meridian of foot- jueyin , the kidney meridian of foot- shaoyin , the stomach meridian of foot- yangming and the conception vessel. The acupoints selected were generally on the lower extremities, the abdomen and the upper extremities. Regarding the special points, the five- shu points and the convergent points were mostly involved. By the analysis on compound prescriptions, 3 patterns of acupoint combination were discovered, the prescription by taking Yingu (KI 10), Rangu (KI 2) and Zhongfeng (LR 4) as the key points, the one by taking Shenshu (BL 23) and Yanggu (SI 5) as the key points and the relevant fixed combination of 4 acupoints, including Taichong (LR 3), Xingjian (LR 2), Neiting (ST 44) and Xiangu (ST 43). By the analysis on the compound prescriptions, 3 common meridian combinations were found, including the combination with the kidney meridian predominated, the relevant fixed combination with the liver meridian and the stomach meridian and the one with small intestine meridian and the lung meridian.

In vitro and in vivo models of Parkinson's disease were established to investigate the effects of the lncRNA XIST/miR-199a-3p/Sp1/LRRK2 axis. The binding between XIST and miR-199a-3p as well as miR-199a-3p and Sp1 were examined by luciferase reporter assay and confirmed by RNA immunoprecipitation analysis. Following the Parkinson's disease animal behavioural assessment by suspension and swim tests, the brain tissue injuries were evaluated by hematoxylin and eosin, TdT-mediated dUTP-biotin nick end labelling, and tyrosine hydroxylase stainings. The results indicated that miR-199a-3p expression was downregulated, whereas that of XIST, Sp1 and LRRK2 were upregulated in Parkinson's disease. Moreover, miR-199a-3p overexpression or XIST knockdown inhibited the cell apoptosis induced by MPP + treatment and promoted cell proliferation. The neurodegenerative defects were significantly recovered by treating the cells with shXIST or shSp1, whereas miR-199a-3p inhibition or Sp1 and LRRK2 overexpression abrogated these beneficial effects. Furthermore, the results of our in vivo experiments confirmed the neuroprotective effects of shXIST and miR-199a-3p against MPTP-induced brain injuries, and the Parkinson's disease behavioural symptoms were effectively alleviated upon shXIST or miR-199a-3p treatment. In summary, the results of the present study showed that lncRNA XIST sponges miR-199a-3p to modulate Sp1 expression and further accelerates Parkinson's disease progression by targeting LRRK2.

Pulmonary aspergillosis (PA), a pulmonary fungal infection caused by Aspergillus spp., is a concern for immunocompromised populations. Despite substantial research efforts, conventional treatments of PA using antifungal agents are associated with limitations such as excessive systemic exposure, serious side effects and limited availability of the therapeutics in the lungs for an adequate duration. To overcome the limitations associated with the conventional regimens, pulmonary delivery of antifungal agents has become a focal point of research because of the superiority of local and targeted drug delivery. Dry powder inhalers and nebulized formulations of antifungal agents have been developed and evaluated for their capability to effectively deliver antifungal agents to the lungs. Moreover, progress in nanotechnology and the utilization of nanocarriers in the development of pulmonary delivery formulations has allowed further augmentation of treatment capability and efficiency. Thus, the following review provides an insight into the advantages and therapeutic potential of the utilization of nanocarriers in pulmonary delivery of antifungal agents for the treatment of PA. In addition, discussions on formulation aspects and safety concerns together with the clinical and regulatory aspects of the formulations are presented, which suggest the possibility and desirability of utilization of nanocarriers in the treatment of PA.

Background: Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma., Methods: Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) were used to search for studies related to the utilization of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma. Literature screening, extraction of data, and evaluation of high standard studies were conducted by 2 independent researchers. The robustness and strength of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic methodology for recurrent high-grade glioma was assessed based on the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). RevMan 5.3 software was used for carrying out the statistical analysis., Results: These results obtained in this study will be published in a peer-reviewed journal., Conclusion: Evidently, the conclusion of this study will provide an assessment on whether combined procarbazine, lomustine, and vincristine provides an effective and safe form of treatment for recurrent high-grade glioma., Systematic Review Registration Number: INPLASY202080078.

The application of special acupoints for different primary symptoms of chronic gastritis in ancient literature of acupuncture and moxibustion was analyzed and summarized. With keywords, electronic and manual retrieval of ancient literature being performed to establish a database, the association rules were performed with SPSS Modeler 18. As a result, ① among all the 2243 items included, 109 items mentioned special acupoints (excluding those only mentioned crossing acupoint). The frequency of special acupoints was 2554 (71.7%), and the special acupoints on the spleen meridian, the stomach meridian, the conception vessel were frequently used. The frequency of five- shu point was highest, followed by front- mu points. ② The special acupoints for four main primary symptoms of chronic gastritis, "stomachache" "vomiting and regurgitation" "belching and acid regurgitation" and "epigastric fullness", included Zusanli (ST 36), Neiguan (PC 6), Zhongwan (CV 12), Gongsun (SP 4), Taibai (SP 3). In addition, the back- shu points were also selected to treat the primary symptoms other than "epigastric fullness". Zhangmen (LR 13) was added to treat "belching and acid regurgitation". The combination of Neiguan (PC 6) and Gongsun (SP 4) showed the strongest correlation; due to different primary symptoms, the combination had different emphasis.

Resveratrol, a naturally occurring polyphenolic compound, exhibits a neuroprotective role in models of central nervous system diseases, including cerebral ischemia/reperfusion injury. Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that contributes to base excision repair of oxidative DNA damage and redox activation of transcription factors, associated with neuronal survival against hypoxic‑ischemic injury. It was hypothesized that resveratrol protects HT22 cells against oxygen‑glucose deprivation and re‑oxygenation (OGD/R)‑induced injuries through upregulation of APE1. It was demonstrated that resveratrol pretreatment significantly increased the viability of HT22 cells and decreased the release of lactate dehydrogenase (LDH), accompanied by the upregulation of APE1 mRNA, and protein levels, as well as the activity of APE1 under OGD/R conditions. In addition, resveratrol reversed OGD/R‑induced oxidative DNA damage as evidenced by the decreases in the levels of 8‑hydroxy‑2'‑deoxyguanosine and APE sites. However, APE1 knockdown using short hairpin RNA sequence targeting APE1 abolished resveratrol‑elicited beneficent effects against OGD/R‑induced cytotoxicity and oxidative stress. This was indicated by decreased cell viability, superoxide dismutase activity and glutathione levels, and increased LDH release and reactive oxygen species levels. The results of the present study indicate that APE1 contributes to the protective effects of resveratrol against neonatal hypoxic‑ischemic brain injuries, and suggest that DNA repair enzymes, including APE1, may be a unique strategy for neuroprotection against this disease.

BACKGROUND Glucagon-like peptide-1 (GLP-1) has been reported to exert some beneficial effects on the central nervous system (CNS). However, the effect of GLP-1 on cognitive impairment associated with type 2 diabetes is not well known. This study investigated the effect of GLP-1 on ameliorating memory deficits in type 2 diabetic rats. MATERIAL AND METHODS Type 2 diabetic rats were induced by a high-sugar, high-fat diet, followed by streptozotocin (STZ) injection and then tested in the Morris Water Maze (MWM) 1 week after the induction of diabetes. The mRNA expression of Arc, APP, BACE1, and PS1 were determined by real-time quantitative PCR, and the Arc protein was analyzed by immunoblotting and immunohistochemistry. RESULTS Type 2 diabetic rats exhibited a significant decline in learning and memory in the MWM tests, but GLP-1 treatment was able to protect this decline and significantly improved learning ability and memory. The mRNA expression assays showed that GLP-1 treatment markedly reduced Arc, APP, BACE1, and PS1 expressions, which were elevated in the diabetic rats. Immunoblotting and immunohistochemistry results also confirmed that Arc protein increased in the hippocampus of diabetic rats, but was reduced after GLP-1 treatment. CONCLUSIONS Our findings suggest that GLP-1 treatment improves learning and memory deficits in type 2 diabetic rats, and this effect is likely through the reduction of Arc expression in the hippocampus.

Long non-coding RNAs (lncRNAs) are proved as important regulators in many diseases, including multiple cancers. HOXA11antisense RNA (HOXA11-AS) is a novel identified lncRNA associated with cancer progression. However, the role of HOXA11-AS in glioma remains poorly understood and needs to be elucidated. The purpose of this study is to investigate the role and regulating mechanism of HOXA11-AS on gliomagenesis. Expression of HOXA11-AS was significantly up-regulated in glioma tissue and cell lines compared to the adjacent normal tissue and cells. Moreover, patients with high HOXA11-AS expression had a shorter survival time and poorer prognosis than that of lower expression. Loss-of-function experiments revealed that HOXA11-AS knockdown inhibited the proliferation, induced cell cycle arrest at G0/G1 phase and enhanced the apoptosis. Bioinformatics prediction forecast that miR-140-5p directly targeted HOXA11-AS at 3'-UTR, which was confirmed by luciferase reporter assay. In vitro rescue experiment assays, miR-140-5p inhibitor transfection could reverse the function of HOXA11-AS knockdown on the proliferation, cell cycle arrest and apoptosis. Together, present study illustrates that the pathway of HOXA11-AS sponging miR-140-5p might play a vital regulating role in the development and progression of glioma.

Objective: To investigate the effect of glucagon-like peptide 1 (GLP-1) on cognitive dysfunction in diabetic rats., Methods: Male SD rats were randomly divided into normal control group, diabetes mellitus (DM) group, and GLP-1 treatment group. Rat models of type 2 diabetes were established by high-sugar and high-fat feeding and streptozotocin (STZ) injection, and 25 days after the onset of diabetes, GLP-1 was infused in GLP-1 treatment group at the rate of 30 pmol·kg -1 ·min -1 via a subcutaneous osmotic pump for 7 days. The learning and cognitive ability of the rats was assessed with Morris water maze test, and the expression of cognition-related genes in the hippocampus tissue was detected with real-time PCR, Western blotting and immunohistochemical staining., Results: Compared with the normal control group, the diabetic rats showed significantly decreased learning and memory abilities (P<0.05) with increased hippocampal expressions of APP, BACE1, Arc, ERK1/2, PKA, and PKC mRNAs (P<0.05) and Arc protein. Compared with diabetic rats, GLP-1-treated rats showed significantly improvements in the learning and memory function (P<0.05) with decreased expressions of APP, BACE1, Arc, ERK1/2, and PKA mRNAs (P<0.05) and Arc protein., Conclusion: GLP-1 can improve cognitive dysfunctions in diabetic rats possibly by regulating the PKC, PKA, and ERK1/2 pathways and inhibiting Arc expression in the hippocampus.

Silver is an alternative antimicrobial of interest for the prophylaxis of prosthetic infections and electrical activation is known to augment its oligodynamic efficacy. In this study, we evaluated the in vitro and in vivo efficacy of a silver (Ag)-titanium (Ti) implant activated by 30 µA direct current compared with three controls - passive Ag-Ti, active Ti-Ti, and passive Ti-Ti. We hypothesized that the experimental group would provide better resistance to pathogenic colonization on the implant. Modified Kirby-Bauer technique was used to evaluate in vitro efficacy of the four groups against five bacteria and one fungus. For in vivo evaluation, forty-eight rats were divided into four groups. The implant was secured in a wound cavity along the posterior margin of the femur. The wound was inoculated with 7.5 × 10(5) CFU of Staphylococcus aureus. Rats were euthanized 14 days postsurgery and quantitative cultures were performed on the implant segments and the wound cavity tissue. In vitro tests showed that the growth of all six pathogens was inhibited around the active Ag anodes of the experimental group. In vivo, none of the four groups were able to prevent wound infection, but the experimental group resulted in reduced colonization. The mean bacterial loads on Ti segments were significantly lower in the implants which also had an Ag segment (p = 0.0007), and this effect was more pronounced with electrical activation (p = 0.0377). The results demonstrate the antimicrobial potential of LIDC-activated Ag-Ti implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1023-1031, 2016., (© 2015 Wiley Periodicals, Inc.)

Isolated cerebral varix is a rare cerebrovascular anomaly, which is easily misdiagnosed as other brain tumors.A 59-year-old female patient with noncontributory medical history presented with headache and insomnia for the last 2 months. Upon admission, her neurological examination was unremarkable. Magnetic resonance imaging revealed a well-demarcated extra medullary mass, 11 × 11 mm in size, within the subdural space at the right frontal lobe. The lesion was initially interpreted as a convexity meningioma. After conducting a craniotomy on the patient, an extra-axial varix was exposed and resected subsequently. The patient's headache was resolved soon after surgery and charged without neurologic sequelae.Extra-axial isolated cerebral varix is mimicking convexity meningioma on MR images and should be considered as a differential diagnosis. The focal erosion in the inner table of the skull could be an important character of extra-axial isolated cerebral varix. An extremely round shape and smooth contour of the lesion was another important character. Isolated cerebral varix is rare vascular lesion that is treated surgically in the case of rupture or compression of adjacent structures. The information obtained with noninvasive imaging techniques should include CTA to make a clinical decision.

Considerable progress has been made increasing productivity of cell cultures to meet the rapidly growing demand for antibody biopharmaceuticals through increased cell densities and longer culture times. This in turn has dramatically increased the burden of process and product related impurities on the purification processes. In addition, current trends in the biopharmaceutical industry point toward both increased productivity and targeting smaller patient populations for new indications. Taken together, these developments are driving the industry to explore alternative separation technologies as a future manufacturing strategy. Clarification technologies well established in other industries, such as flocculation and precipitation are increasingly considered as a viable solution to address this bottleneck in antibody processes. However, several technical issues need to be fully addressed including suitability as a platform application, robustness, process cost, toxicity, and clearance. This review will focus on recent efforts to incorporate new generation clarification technologies for mammalian cell cultures producing monoclonal antibodies as well as challenges to their implementation supported by a case study., (© 2015 Wiley Periodicals, Inc.)

Aim: To obtain a correlation between HER-2 expression and the clinicopathological features incolorectal cancers. (CRCs) using a meta.analysis based approach., Materials and Methods: Electronic databases and reference lists were searched for relevant published studies. After inclusion and exclusion criteria were applied, case and control studies related to research topic were included in present meta-analysis. Data analysis was performed using Comprehensive Meta Analysis. (CMA) 2.0 software., Result: A total of 30 studies comprising 4,942 CRC patients and 521 healthy controls met the inclusion criteria. Our major results implied that the expression level of HER-2 was significantly higher in CRC patients than healthy controls (odds ratio (OR) = 10.436, 95% confidence interval (CI) = 5.498-19.810, P < 0.001). Sample stratification based on Dukes stages suggested that increased expression level of HER-2 protein was found in CRC patients with Dukes C/D compared with CRC patients with Dukes A/B (OR = 0.335, 95% CI = 0.198-0.568, P < 0.001). The current meta-analysis also found that, in CRC patients with lymph node metastasis (LNM), the HER-2 expression was significantly higher than that in CRC patients without LNM (OR = 1.987, 95%CI = 1.209-3.265, P = 0.007)., Conclusion: Our meta-analysis study strongly suggests that HER-2 expression levels are clearly correlated with the clinicopathological features in CRC; therefore, HER-2 may be a potential biomarker for diagnosis and prognosis of CRC.

Aim: To investigate the correlation between human epidermal growth factor receptor (HER-2) protein expression and colorectal cancer (CRC) using a case-control study and meta-analysis., Methods: Tumor tissue specimens from 162 CRC patients were selected for the case group. Fifty cases were randomly selected, and normal CRC tissue at least 10 cm away from the tumor margins of these cases was used to generate the control group. The expression of the HER-2 protein in the 162 CRC tissue samples and the 50 adjacent normal mucosa tissue samples was detected via immunohistochemistry. The experimental data were analyzed using SPSS 18.0 software, and R software version 3.1.0 was utilized for further verification., Results: The expression of HER-2 protein in the 162 CRC tissue samples was significantly higher than in the normal tissue specimens. The data showed that the expression of HER-2 in CRC was related to the Dukes' stage, the depth of invasion and lymph node metastasis. The HER-2-positive patients had lower 3- and 5-year OS rates than the HER-2-negative patients, but there was no significant difference. However, there was a statistically significant difference in the 3- and 5-year disease-free survival (DFS) rates of HER-2-positive and HER-2-negative patients. The results of the meta-analysis showed that the expression of HER-2 in CRC patients was statistically significantly increased over that of healthy people. The 3-year DFS rate in HER-2-positive patients was markedly lower than that in HER-2-negative patients., Conclusion: Down-regulation of HER-2 expression might be a dependable strategy for CRC therapy.

The gene encoding the GroEL chaperonin is duplicated in nearly 30% of bacterial genomes; and although duplicated groEL genes have been comprehensively determined to have distinct physiological functions in different species, the mechanisms involved have not been characterized to date. Myxococcus xanthus DK1622 has two copies of the groEL gene, each of which can be deleted without affecting cell viability; however, the deletion of either gene does result in distinct defects in the cellular heat-shock response, predation, and development. In this study, we show that, from the expression levels of different groELs, the distinct functions of groEL1 and groEL2 in predation and development are probably the result of the substrate selectivity of the paralogous GroEL chaperonins, whereas the lethal effect of heat shock due to the deletion of groEL1 is caused by a decrease in the total groEL expression level. Following a bioinformatics analysis of the composition characteristics of GroELs from different bacteria, we performed region-swapping assays in M. xanthus, demonstrating that the differences in the apical and the C-terminal equatorial regions determine the substrate specificity of the two GroELs. Site-directed mutagenesis experiments indicated that the GGM repeat sequence at the C-terminus of GroEL1 plays an important role in functional divergence. Divergent functions of duplicated GroELs, which have similar patterns of variation in different bacterial species, have thus evolved mainly via alteration of the apical and the C-terminal equatorial regions. We identified the specific substrates of strain DK1622's GroEL1 and GroEL2 using immunoprecipitation and mass spectrometry techniques. Although 68 proteins bound to both GroEL1 and GroEL2, 83 and 46 proteins bound exclusively to GroEL1 or GroEL2, respectively. The GroEL-specific substrates exhibited distinct molecular sizes and secondary structures, providing an encouraging indication for GroEL evolution for functional divergence., Competing Interests: The authors have declared that no competing interests exist.

Objective: To study the chemical constituents contained in the seeds of Cucumis sativus., Method: The fatty oil was extracted by heating and refluxing with petroleum ether. Potassium hydroxide-methanol solution was used for saponification. An unsaponifiable matter was extracted by EtOAc and separated with various chromatographic methods. Its structure was identified on the basis of their physicochemical properties and spectral data. The fatty acid fraction was methyl-esterified and determined by GC. The composition and relative content of fatty acid were determined with normalization method of peak area., Result: 24-ethylcholesta-7, 22, 25-trienol (1), 24-ethylcholesta-7, 25-dienol (2) ,avenasterol (3), spinasterol (4), karounidiol (5) and isokarounidiol (6) were separated and identified from the unsaponifiable matter. Myristic acid (7, 0.12%), palmitic acid (8, 12.04%), palmitoleic acid (9, 0.09%), heptadecanoic acid (10, 0.06%), stearic acid (11, 5.64%), oleic acid (12, 6.95%), linoleic acid (13, 74.40%), arachidic acid (14, 0.19%), and alpha-linolenic acid (15, 0.51%) were identified from the fatty acids part., Conclusion: Compounds 5, 6, 9, 10, 14,and 15 were first reported in C. sativus.

Myxococcus fulvus HW-1, a salt-tolerant bacterial strain, which was isolated from a coastal environment, changes its behavior with different salinities. To study the relationship between behavioral shifts and the adaption to oceanic conditions, the HW-1 strain was randomly mutagenized using transposon insertion, producing a dispersed-growing mutant, designated YLH0401. The mutant did not develop fruiting bodies and myxospores, was deficient in S-motility, produced less extracellular matrix and was less salt tolerant. The YLH0401 strain was determined to be mutated by a single insertion in a large gene of unknown function (7011 bp in size), which is located in a horizontally transferred DNA fragment. The gene is expressed during the vegetative growth stage, as well as highly and stably expressed during the development stage. This horizontally transferred gene may allow Myxococcus to adapt to oceanic conditions.

A RF coil (or probe) is one of the key components in NMR spectrometers and MRI systems, and designing a quality RF coil is a cheaper way to improves the signal-to-noise ratio (SNR) of systems and image quality. According to different applications there are a variety of RF coils. This article describes high-sensitive micro RF coils used in NMR spectrometers specially for test-tube samples. Their performance has been verified on the desktop MRI systems.