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Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients. Glioblastoma cell lines over-expressing IL-11Rα displayed greater survival, proliferation, migration and invasion in glucose-free conditions compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα reversed these pro-tumorigenic characteristics. In addition, these IL-11Rα-over-expressing cells displayed enhanced glutamine oxidation and glutamate production compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα or the pharmacological inhibition of several members of the glutaminolysis pathway resulted in reduced survival (enhanced apoptosis) and reduced migration and invasion. Furthermore, IL-11Rα expression in glioblastoma patient samples correlated with enhanced gene expression of the glutaminolysis pathway genes GLUD1, GSS and c-Myc. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell survival and enhances cell migration and invasion in environments of glucose starvation via glutaminolysis.

The purpose of this research is to examine the effect of price and product completeness on purchasing decisions. This research was conducted quantitatively, with a causal type. The population of this research is buyers in B2 Variasi Motor Jombang. Hypothesis testing uses the t test and f test, and uses the R2 test and multiple linear regression analysis. The results showed that: 1) Price partially affects the Purchase Decision, resulting in a probability value of 0.00. 2) Product completeness partially affects the purchasing decision resulting in a probability value of 0.00. 3). Meanwhile, price and product completeness have a simultaneous effect on purchasing decisions, with a probability value of 0.00. Keywords: Price, Product Completeness, Buying Decision

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.

Simple Summary A key molecule, EGFRvIII has been shown to provide several growth advantages for brain tumors. However, we have found a new mechanism in which the EGFRvIII provides increased survival to brain cancer cells when under sub-optimal conditions. Specifically, we have found that the EGFRvIII drives the expression of a molecule called Reticulocalbin 1 (RCN1) and that RCN1 blocks cell stress and cell death, thereby allowing cells to survive and proliferate. Importantly, these findings will allow for the generation of drugs that block the function of EGFRvIII and RCN1 with the hope that these drugs will induce brain cancer cell death. Abstract Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.

Artikel ini secara umumnya mengkaji metodologi ulama hadis mutaqaddimīn dalam penerimaan hadis tafarrud. Dalam hal ini, kajian ditumpukan kepada Aḥmad ibn Ḥanbal. Menurut Ibn Rajab al-Ḥanbalī, Aḥmad dan kebanyakan ulama mutaqaddimīn menjadikan tafarrud sebagai tanda kewujudan ʿIllah padanya. Justeru, kajian ini bertujuan menjelaskan tiga aspek utama, iaitu konsep tafarrud menurut ahli hadis, ketokohan Aḥmad ibn Ḥanbal dalam ilmu hadis serta menganalisis metodologi beliau dalam penerimaan hadis tafarrud. Kajian ini berbentuk kualitatif dan dijalankan dengan menggunakan metod kajian kepustakaan. Data kajian diambil daripada kitab al-Muntakhab Min al-ʿIlal Li al-Khallāl yang mengumpulkan pandangan Aḥmad bin Ḥanbal. Data tersebut seterusnya dianalisis secara induktif untuk mengeluarkan metodologi yang diamalkan oleh Aḥmad ibn Ḥanbal dalam penerimaan hadis tafarrud. Hasil kajian mendapati Aḥmad ibn Ḥanbal tidak menerima hadis tafarrud secara pukul rata. Sebaliknya, beliau mengesahkannya dengan penuh kehati-hatian berdasarkan kewujudan qarā’in yang terdapat pada hadis.

Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.

Acute pancreatitis related to mumps infection is rarely reported. In this case report, we highlight a case of acute pancreatitis caused by mumps infection in adulthood. A 25-year old woman treated for mumps developed sudden onset of vomiting and epigastric pain. She had an elevation of serum amylase and was treated for acute pancreatitis. She showed remarkable improvement of clinical symptoms with supportive treatment and after her bilateral parotid swelling receded.International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 Page: 261-263

The epoxidized vegetables oils can be used a raw material for a broad range of products, from pharmaceutical and plastics to paint and adhesives. Epoxidation of oleic acid was carried out by using hydrogen peroxide as an oxygen donor and formic acid as an oxygen carrier in the presence of sulphuric acid act as catalyst. The crude oleic acid contained 75% oleic acid, 12.2% linoleic acid, 6.5% palmitic acid and 7.5% stearic acid, and had an iodine value of 98.99 g/100 g. The epoxidation of oleic acid with almost complete conversion of unsaturated carbon and negligible oxirane cleavage can be obtained by the in situ techniques. An analytical approach for the prediction of the partition coefficient for formic acid between oleic acid and water, dependent on temperature and composition, has been proposed.

Aim of this research is to investigate the ability of synergist system of D2EHPA-isodecanol to recover gold from thiourea leaching solution. Synergistic extraction was introduced to replace single extraction due to enhance the extraction efficiency of heavy metal such as gold, silver copper and etc. In order to improve extraction efficiency, di-(2ethylhexyl) phosphoric acid (D2EHPA) was mixed with isodecanol to provide synergistic effect together with leaching solution which thiourea. From the synergist extraction system. The optimum pH is at 2.5 which in acidic range producing the highest yield of %E of 94.6%. It was found that synergistic D2EHPA-isodecanol extraction is successful as it yield %E of 99.4% if the ratio aqueous: organic is set to 1:2.

Heterotrigona itama is a common stingless bee species found in Southeast Asia. Studies on the health benefits of its honey are limited in comparison with other stingless bee species. This study examines the antiobesity benefits found in stingless bee honey (SBH) from H. itama. The parameters used to measure the benefits were weight change, morphological structures, and biochemical characteristics. The research was conducted by using rats that were given a high-fat diet (HFD). In total 48 male Sprague Dawley (SD) rats were given a formulated HFD to increase the levels of obesity, the HFD was administered with a value of 0.68 g/cm2. The duration of the treatment was six weeks, and the results show that the induction obesity using the HFD was successful. Following this, the rats were then treated with SBH (at dosages of 1000 mg/kg, 750 mg/kg or 500 mg/kg), with orlistat or with a placebo. Compared with typical obesity treatment methods, the one that used the three dosages of SBH showed a higher reduction in body mass index (BMI), percentage of body weight gain, adiposity index, and relative organ weight (ROW). The levels of liver enzymes (ALT, AST, and ALP) were also significantly lower in SBH-treated groups. The levels of triglycerides and LDL-cholesterol were significantly lower, while the level of HDL-cholesterol was significantly higher in comparison with the control obese group. In terms of morphological structures, the number of adipocyte cells was reduced, and the hepatocytes found in the liver were less prone to rupturing when treated with SBH. In conclusion, the administration of SBH led to an improvement in indicators associated with obesity reduction. SBH also possesses a hepatoprotective potential which can reduce the health risks related to obesity.

Heterotrigona itama is a common stingless bee species found in Southeast Asia. Studies on the health benefits of its honey are limited in comparison with other stingless bee species. This study examines the antiobesity benefits found in stingless bee honey (SBH) from H. itama. The parameters used to measure the benefits were weight change, morphological structures, and biochemical characteristics. The research was conducted by using rats that were given a high-fat diet (HFD). In total 48 male Sprague Dawley (SD) rats were given a formulated HFD to increase the levels of obesity, the HFD was administered with a value of 0.68 g/cm2. The duration of the treatment was six weeks, and the results show that the induction obesity using the HFD was successful. Following this, the rats were then treated with SBH (at dosages of 1000 mg/kg, 750 mg/kg or 500 mg/kg), with orlistat or with a placebo. Compared with typical obesity treatment methods, the one that used the three dosages of SBH showed a higher reduction in body mass index (BMI), percentage of body weight gain, adiposity index, and relative organ weight (ROW). The levels of liver enzymes (ALT, AST, and ALP) were also significantly lower in SBH-treated groups. The levels of triglycerides and LDL-cholesterol were significantly lower, while the level of HDL-cholesterol was significantly higher in comparison with the control obese group. In terms of morphological structures, the number of adipocyte cells was reduced, and the hepatocytes found in the liver were less prone to rupturing when treated with SBH. In conclusion, the administration of SBH led to an improvement in indicators associated with obesity reduction. SBH also possesses a hepatoprotective potential which can reduce the health risks related to obesity.

Polymer Dielectric Materials

The objective of this cross-sectional study is to determine the prevalence and pattern of herbal medicines use during pregnancy among women in Tumpat district, Kelantan. A total of 210 mothers were interviewed using a structured questionnaire. There were 108 mothers (51.4%) who used at least one type of herbal medicines during pregnancy. The most common herbal medicines used (63.9%) was coconut oil which was ingested during the third trimester of pregnancy only. The most common indication was (89.8%) to facilitate labour. The majority of users (79.6%) used herbal medicines during the third trimester of pregnancy only. Many of them (81.5%) believed that herbal medicines were effective to solve their health problems and fulfilled the indications for use. The older generation like parents and in laws (63.9%) were the most common persons who suggested using herbal medicines. The majority of them used the herbs only once (56.5%) and one type (87.0%) throughout the pregnancy. Further research focusing on local commonly used herbal medicines is to be carried out to evaluate the safety and efficacy of the herbs.