Introduction: The mortality rate of glioma patients particularly with glioblastoma multiforme (GBM) remains high even with advancements in the multimodality treatment. This is partly due to chemoresistance of the glioma cells towards drug treatment which finally reduced the survival of GBM patients. In this study, we determined the chemosensitisation and oncogenic characteristics of ZFP36L2 in LN18 GBM cells using RNA interference (RNAi). Methods: Meta-analysis of microarray datasets was used to identify the druggable genes responsive to GBM chemosensitivity. Subsequently, the genes were validated using RNAi screening [pooled small interference RNA (siRNA)]. Temozolomide- resistant LN18 cells were used to evaluate the effects of gene silencing on chemosensitisation to the sub-lethal dose (1/10 of IC50) of temozolomide. Assays such as cell viability, proliferation, migration and invasion and apoptosis assays were carried out. The apoptosis pathway underlying chemosensitisation by ZFP36L2 siRNA was determined using a human apoptosis array kit. Statistical analyses were performed using one-way analysis of variance. Results: ZFP36L2 was identified as a potential marker of GBM based on the meta-analysis and RNAi screening. ZFP36L2 knockdown lead to 1) Apoptosis induction (p < 0.05) 2) Reduced cell migration (p < 0.05) 3) Reduced up to 82% of cell invasion (p < 0.01) and 4) Decreased cellular proliferation in siZFP36L2-treated LN18 cells. Downstream analysis showed that the sub-lethal dose of temozolomide caused major upregulation of BCL2-associated X, apoptosis regulator (BAX). Conclusion: ZFP36L2 is oncogenic and chemosensitive thus may contribute to gliomagenesis through cell proliferation, migration, invasion and apoptosis. RNAi therapy in combination with chemotherapy treatment such as temozolomide may serve as potential therapeutic approach in the future.
PIP: Previous studies have shown the users of intrauterine devices have a 4.4 times greater risk of pelvic inflammatory disease. This present study intends to categorize the distribution of microbes in cultures from different types of extracted copper intrauterine devices (IUCDs). Bacteriological studies of aerobic and anaerobic organisms were performed on the extracted IUCDs of 522 IUCD users; 480 wearing a Multiload Cu 250, 15 wearing a Copper T, 22 Lippes Loop and 5 a Copper 7. Cultures were negative in 46 (8.8%) IUCD cultures where 43 were Multiloads, Copper T (1) and Lippes Loop (2). 91.2% yielded bacterial growth and the commonest organisms isolated were Staphylococcus species, (23%), E.coli (9.6%) and Staphylococcus aureus (4.0%. Candida albicans, E.coli and Staphylococcus sp. were commonly isolated from Multiload, Copper T, Lippes Loop and Copper 7. Beta-hemolytic streptococci, Staphylococcus aureus and Candida sp. were frequently recovered from Multiload, Copper T and Lippes Loop. Only Multiload cultures yielded Bacillus, Streptococcus viridans, Klebsiella, Proteus, Enterobacter, Citrobacter diversus, Citrobacter freundii, Moraxella, Pseudomonas and Acinetobacter. One woman with complaint of PID yielded E.coli in her IUCD culture.
Effective optimization of microalgae-to-bioethanol process systems hinges on an in-depth characterization of key process parameters relevant to the overall bioprocess engineering. One of the such important variables is the biomass particle size distribution and the effects on saccharification levels and bioethanol titres. This study examined the effects of three different microalgal biomass particle size ranges, 35 μm ≤ x ≤ 90 μm, 125 μm ≤ x ≤ 180 μm, and 295 μm ≤ x ≤ 425 μm, on the degree of enzymatic hydrolysis and bioethanol production. Two scenarios were investigated: single enzyme hydrolysis (cellulase) and double enzyme hydrolysis (cellulase and cellobiase). The glucose yield from biomass in the smallest particle size range (35 μm ≤ x ≤ 90 μm) was the highest, 134.73 mg glucose/g algae, while the yield from biomass in the larger particle size range (295 μm ≤ x ≤ 425 μm) was 75.45 mg glucose/g algae. A similar trend was observed for bioethanol yield, with the highest yield of 0.47 g EtOH/g glucose obtained from biomass in the smallest particle size range. The results have shown that the microalgal biomass particle size has a significant effect on enzymatic hydrolysis and bioethanol yield.
Subcritical water extraction (SCW) was used to extract oil from Chlorella pyrenoidosa. The operational factors such as reaction temperature, reaction time, and biomass loading influence the oil yield during the extraction process. In this study, response surface methodology was employed to identify the desired extraction conditions for maximum oil yield. Experiments were carried out in batch reactors as per central composite design with three independent factors including reaction temperature (170, 220, 270, 320, and 370°C), reaction time (1, 5, 10, 15, and 20 min), and biomass loading (1, 3, 5, 10, and 15%). A maximum oil yield of 12.89 wt.% was obtained at 320°C and 15 min, with 3% biomass loading. Sequential model tests showed the good fit of experimental data to the second-order quadratic model. This study opens the great potential of SCW to extract algal oil for use in algal biofuel production.
Palm oil mill effluent (POME) has high chemical oxygen demand (COD), thus requires effective treatments to environmentally benign levels before discharge. In this study, immobilized microalgae cells are used for removing pollutants in treated palm oil mill effluent (TPOME). Different ratios of microalgae beads to TPOME concentration were examined at 1:2.5, 1:5, and 1:10. The biomass concentration and COD removal were measured through a standard method. The color of the cultivated microalgae beads changed from light green to darker green after the POME treatment for 9 days, hence demonstrating that microalgae cells were successfully grown inside the beads with pH up to 9.84. The immobilized cells cultivated in the POME at 1:10 achieved a higher biomass concentration of 1.268 g/L and a COD removal percentage of 72% than other treatment ratios. The increment of the ratio of microalgae cells beads to POME concentration did not cause any improvement in COD removal efficiency. This was due to the inhibitory effect of self-shading resulting in the slow growth rate of microalgae cells which responsible for low COD removal. Therefore, this system could be a viable technology for simultaneous biomass production and POME treatment. This will contribute to research efforts toward the development of new and improved technologies in treating POME.
Global warming has become a serious issue nowadays as the trend of CO2 emission is increasing by years. In Malaysia, the electricity and energy sector contributed a significant amount to the nation's CO2 emission due to fossil fuel use. Many research works have been carried out to mitigate this issue, including carbon capture and utilization (CCUS) technology and biological carbon fixation by microalgae. This study makes a preliminary effort to screen native microalgae species in the Malaysian coal-fired power plant's surrounding towards carbon fixation ability. Three dominant species, including Nannochloropsis sp., Tetraselmis sp., and Isochrysis sp. were identified and tested in the laboratory under ambient and pure CO2 condition to assess their growth and CO2 fixation ability. The results indicate Isochrysis sp. as the superior carbon fixer against other species. In continuation, the optimization study using Response Surface Methodology (RSM) was carried out to optimize the operating conditions of Isochrysis sp. using a customized lab-scale photobioreactor under simulated flue gas exposure. This species was further acclimatized and tested under actual flue gas generated by the power plant. Isochrysis sp. had shown its capability as a carbon fixer with CO2 fixation rate of 0.35 gCO2/L day under actual coal-fired flue gas exposure after cycles of acclimatization phase. This work is the first to demonstrate indigenous microalgae species' ability as a carbon fixer under Malaysian coal-fired flue gas exposure. Thus, the findings shall be useful in exploring the microalgae potential as a biological agent for carbon emission mitigation from power plants more sustainably.
Intraorbital foreign body (IOFB) has been a rare phenomenon in the cases of gunshot wounds and always represents a dilemma in medical management. In Sabah, this scenario is becoming common as there is still certain population in the interiors who owns self made guns for hunting. They either present with self inflicted gunshot injuries or after being mistakenly shot while hunting. There are very few articles on this topic especially when it is located posteriorly in the orbit and occurs without visual impairment. This case reports the challenges faced in the management of the patient with a posteriorly located metallic IOFB. The appropriate management of the patient is discussed based on several international literatures. Author describes a 37 years old male farmer, who was referred from a nearby district hospital after he sustained gunshot injuries to his face and scalp. Urgent computed tomography (CT) scan showed that bullet pellets were at the left orbital floor, the left mandible and the left frontal bone. All bullet pellets were located extracranially only without intracranial involvement. Patient clinically does not have any neurologic deficit and without any visual impairment, thus he refused any surgical intervention. As there is no proper guideline in managing such cases, decision was made based on evidences from international literatures. It was concluded that metallic IOFB located in the posterior orbit may be conservatively managed with observation and regular follow-ups as they are well-tolerated and does not cause much impact on visual deterioration unless inflammation, infection, optic neuropathy or functional deficit occurs. This avoids unnecessary surgery and prevents risk of iatrogenic injury to the eye.
This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. Nine SNPs spanning the HNF4 alpha P2 promoter (rs4810424, rs1884613 and rs1884614) and coding region (rs2144908, rs6031551, rs6031552, rs1885088, rs1028583 and rs3818247) were genotyped in 160 subjects without diabetes or metabolic syndrome. The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). The intron 1D SNP rs2144908 was associated with high-density lipoprotein cholesterol (HDLc) (p = 0.020) and the intron 9 SNP rs3818247 showed association with systolic (p = 0.02) and diastolic (p = 0.034) blood pressure. HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus.
One hundred patients with carcinoma of the cervix stages 1B to 4A were treated with intracavitary high dose rate radiation using a linear cobalt source. All cases have received external beam pelvic irradiation to 4500cGy mid plane in twenty fractions over four weeks. The results in terms of patient compliance and convenience were good while acute and late morbidities were comparable to standard Manchester technique of low dose rate intracavitary therapy as practised in the Institute of Radiotherapy and Oncology General Hospital Kuala Lumpur. The four year actuarial survival rate is 76% for stage II and 48% for stage III. All three stage IV patients died within 1 year. Four out of seven stage I patients are alive (minimum follow-up 18 months, longest 43 months). One died of systemic spread at 33 months while one is lost to follow up.
The interest in utilizing algae for wastewater treatment has been increased due to many advantages. Algae-wastewater treatment system offers a cost-efficient and environmentally friendly alternative to conventional treatment processes such as electrocoagulation and flocculation. In this biosystem, algae can assimilate nutrients in the wastewater for their growth and simultaneously capture the carbon dioxide from the atmosphere during photosynthesis resulting in a decrease in the greenhouse gaseousness. Furthermore, the algal biomass obtained from the treatment process could be further converted to produce high value-added products. However, the recovery of free suspended algae from the treated effluent is one of the most important challenges during the treatment process as the current methods such as centrifugation and filtration are faced with the high cost. Immobilization of algae is a suitable approach to overcome the harvesting issue. However, there are some drawbacks with the common immobilization carriers such as alginate and polyacrylamide related to low stability and toxicity, respectively. Hence, it is necessary to apply a new carrier without the mentioned problems. One of the carriers that can be a suitable candidate for the immobilization is zeolite. To date, various types of zeolite have been used for the immobilization of cells of bacteria and yeast. If there is any possibility to apply them for the immobilization of algae, it needs to be considered in further studies. This article reviews cell immobilization technique, biomass immobilization onto zeolites, and algal immobilization with their applications. Furthermore, the potential application of zeolite as an ideal carrier for algal immobilization has been discussed.
Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that commonly exhibits resistance to treatment. The tumour is highly heterogenous and complex kinomic alterations have been reported leading to dysregulation of signalling pathways. The present study aimed to investigate the novel kinome pathways and to identify potential therapeutic targets in GBM. Meta‑analysis using Oncomine identified 113 upregulated kinases in GBM. RNAi screening was performed on identified kinases using ON‑TARGETplus siRNA library on LN18 and U87MG. Tousled‑like kinase 1 (TLK1), which is a serine/threonine kinase was identified as a potential hit. In vitro functional validation was performed as the role of TLK1 in GBM is unknown. TLK1 knockdown in GBM cells significantly decreased cell viability, clonogenicity, proliferation and induced apoptosis. TLK1 knockdown also chemosensitised the GBM cells to the sublethal dose of temozolomide. The downstream pathways of TLK1 were examined using microarray analysis, which identified the involvement of DNA replication, cell cycle and focal adhesion signalling pathways. In vivo validation of the subcutaneous xenografts of stably transfected sh‑TLK1 U87MG cells demonstrated significantly decreased tumour growth in female BALB/c nude mice. Together, these results suggested that TLK1 may serve a role in GBM survival and may serve as a potential target for glioma.
Microalgae are a promising source of omega-3. The purpose of this study was to extract lipid with a relatively high content of eicosapentaenoic acid (EPA) from Nannochloropsis gaditana using subcritical water extraction (SWE). The effects of different temperatures (156.1-273.9°C), extraction times (6.6-23.4 minutes), and biomass loadings (33-117 g algae/L) on the extraction yield were studied. From the optimization study using central composite design (CCD), quadratic models generated for lipid yield and EPA composition were considered to be significant models (p < 0.05). The predictive equations were also formed for lipid yield and EPA composition. The predicted optimum lipid yield and EPA composition at 236.54°C, 13.95 minutes, and 60.50 g algae/L were 18.278 wt% of total biomass and 14.036 wt% of total fatty acid methyl ester (FAME), respectively.
This research aimed to improve the stability of Chlorella-Alginate Beads (CABs) by zeolite molecular sieves 13X. Dissolution time of synthesized Zeolite-Algal-Alginate Beads (ZABs) in a chelating agent revealed a significant improvement on the beads stability (78.5 ± 0.5 min) compared to the control beads (51.5 ± 0.5 min) under the optimum conditions of zeolite/alginate (1.5:1), pH 5 and 2% of beads. Monitoring cell growth during 5 days of incubation showed good biocompatibility of zeolite 13X. Scanning electron microscopy (SEM) indicated rough surface and spherical shapes of ZABs. Energy dispersive X-ray spectroscopy (EDX) and Fourier transform infrared spectroscopy (FTIR) of ZABs confirmed the presence of zeolite 13X within the matrix. The zeta potential value of ZABs indicated that the beads were relatively stable. The findings of this research showed that zeolite molecular sieves 13X have the potential to improve the stability of algal-alginate beads compared to common beads.
We report a rare case of a young female with primary brain fibrosarcoma, and to the best of our knowledge, we believe that only <50 cases have been reported or described worldwide so far. Fibrosarcoma is a malignant neoplasm, in which histologically the predominant cells are fibroblasts that divide excessively without cellular control and they can invade local tissues or metastasize. Primary central nervous system fibrosarcomas are very aggressive neoplasms and generally have a poor prognosis. This tumor is either from sarcomatous transformation of a meningioma or arises de novo within the brain parenchyma. Our patient, a 48-year-old woman, who presented with progressive speech disorder over the period of 4 months, showed a left temporoparietal lesion with surrounding edema and local mass effect. Total surgical resection was achieved. Histopathology revealed classical fibrosarcoma features and secondary screening revealed no other distant lesion as diagnosis of primary brain fibrosarcoma was established. This case is deemed to be extremely rare because most reports claim that recurrence is within 6 months with poor prognosis; however, this patient is currently recurrence-free at 3 years. This would suggest of the possibility for a relook into this disease's course and recurrence rate when complete excision is achieved. Due to extreme rarity of these tumors, more comparative studies will be needed to improve the disease outcome.
Healthcare costs continue to rise every day as the demand outgrows the supply of surgeons. The application of telephone consultation for immediate management is needed as most neurosurgeons are technology orientated. This enables a specialist at a remote mobile site to receive the necessary information and reduce transmission time, from the second the patient is seen till the management is obtained.
Metastatic tumors are the most common mass lesions in the brain. This case reports a rare form of sarcoma with metastasis to the brain. The appropriate management of a patient with metastatic alveolar soft part sarcoma to the brain is discussed. Author describes a 32-year-old gentleman diagnosed with primary tumor at gluteus and distant metastases at lower lobe of right lung and the brain. Histopathology proves diagnosis as alveolar soft part sarcoma. Craniotomy with excision of brain lesion was done. Repeated magnetic resonance imaging of the brain after 2 months showed rapidly growing new lesions. The next step of management was made by the oncology team as recurrence rate was high and due to multi-systemic involvement. Patient was planned for palliative chemotherapy and to be reassessed later. This case report discusses the appropriate approach to any form of brain metastases and the role of early follow-up especially after surgery for better outcome and choice of post operative management such as radiotherapy or chemotherapy or both for malignant tumors. Based on this report, it was concluded that every brain tumor patient should be frequently monitored even in the outpatient setting as most of them are metastatic and rapidly spreading. The patient should be considered for radiotherapy or chemotherapy or both after surgery if the histopathology result is suggestive of malignancy.
Context: Hydrocephalus, due to subarachnoid or intraventricular hemorrhage (IVH), meningitis, or tumor compression, is usually transient and may resolve after treatment. There are several temporary methods of cerebrospinal fluid (CSF) diversion, none of it is superior to the other, and the decision is based on its various etiologies and factors. Ventriculosubgaleal shunt (VSGS) is one of those temporary measures, which is a simple and rapid CSF decompression method without causing electrolyte and nutritional losses.
Aims: The aim is to study the efficacy of VSGS for temporary CSF diversion, compared to extraventricular drainage (EVD) in adult hydrocephalus patients; to evaluate the outcome in terms of avoiding a permanent shunt, and to look for incidences of their complications.
Settings and Design: This was a retrospective observational study.
Subjects and Methods: The data were acquired from case notes of fifty patients with acute hydrocephalus: 26 secondary to IVH, 10 from aneurysm rupture, 8 posttrauma, and 6 from infection. All these patients had undergone CSF diversion in Hospital Queen Elizabeth II, Sabah, Malaysia, between 2013 and 2015. The patients were followed up from the date of treatment until the resolution of hydrocephalus, where parameters such as shunt dependency and complications were documented.
Statistical Analysis Used: All analyses were carried out using Statistical Packages for the Social Sciences Version 22.0. Chi-squared test or Fisher's exact test is used for univariate analysis of categorical variables.
Results: A total of 21 (42%) patients underwent EVD insertion and 29 (58%) underwent VSGS insertion. Thirty-seven (74%) patients did not require a permanent shunt; 24 (64.8%) of them were from the VSGS group (P = 0.097). EVD had more intracranial complications (44.1%) compared with VSGS (23.5%), with a statistically significant P = 0.026.
Conclusions: VSGS is a safe and viable option for adult hydrocephalus patients, with the possibility of continuation of the treatment for such patients in nonneurosurgical centers, as opposed to patients with EVDs. Furthermore, even though this method had no statistical difference in avoiding a permanent ventriculoperitoneal shunt, VSGS has statistically significant less intracranial complications compared with EVD.
Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.