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The COVID-19 pandemic and the lockdown measures have taken a toll on every level of the society, worldwide. This study examines their psychological impact on university students in Asia. A cross-sectional online survey was conducted between April and May 2020 in Malaysia, Saudi Arabia, Pakistan, Bangladesh, China, India and Indonesia. The Zung's self-rating anxiety scale (SAS) and questions on adaptive and maladaptive coping strategies were used in this study. A total of 3,679 students from the seven countries participated in this study. Overall, 21.9% and 13.7% of the students in this study experienced mild to moderate and severe to extreme levels of anxiety. More than 20% of the students from China and Bangladesh reported severe to extreme level of anxiety compared to below 10% of the students from Indonesia, Malaysia and India. Among the female students, 15.9% experienced severe to extreme level of anxiety compared to 10.6% among the males. Females from Bangladesh, China, Malaysia, Pakistan and Saudi Arabia experienced significantly higher levels of anxiety compared to their male counterparts. Acceptance was the most used and Seeking Social Support was the least used coping strategies among the students. There were significant differences in the usage of the four strategies by countries. Stressors are predominantly financial constraints, remote online learning, and uncertainty related to their academic performance, and future career prospects. [ABSTRACT FROM AUTHOR]

Leukemia is a group of cancer caused by the abnormal proliferation and differentiation of hematopoietic stem cells. Efforts geared toward effective therapeutic strategies with minimal side effects are underway. Peptides derived from natural resources have recently gained special attention as alternative chemotherapeutic agents due to their minimal adverse effects. In the present study, the aim was to isolate peptides from garlic (Allium sativum) and investigate their anticancer activity against leukemic cell lines. The protein extract of A. sativum was pepsin‐digested to obtain protein hydrolysate followed by sequential purification methods. A novel anticancer peptide, VKLRSLLCS (VS‐9), was identified and characterized by mass spectrometric analysis. The peptide was demonstrated to significantly inhibit the cell proliferation of MOLT‐4 and K562 leukemic cell lines while exhibiting minimal inhibition against normal PBMC. Particularly, VS‐9 could induce apoptosis and upregulate mRNA levels of caspase 3, caspase 8, caspase 9, and Bax while downregulating Bcl‐2, Bcl‐xL, and Bcl‐w. Molecular docking of VS‐9 with the anti‐apoptotic Bcl‐2 protein family suggested that VS‐9 could bind the binding groove of the BH3 domain on target proteins. Protein–peptide interaction analysis by affinity chromatography and LC‐MS/MS further showed that VS‐9 could bind Bcl‐2 proteins. Results suggest VS‐9 as a potential garlic‐derived novel anticancer peptide possessing apoptosis‐inducing properties against leukemic cell lines via anti‐apoptotic Bcl‐2 protein family. [ABSTRACT FROM AUTHOR]

Sinensetin, a plant-derived polymethoxylated flavonoid found in Orthosiphon aristatus var. aristatus and several citrus fruits, has been found to possess strong anticancer activities and a variety of other pharmacological benefits and promising potency in intended activities with minimal toxicity. This review aims to compile an up-to-date reports of published scientific information on sinensetin pharmacological activities, mechanisms of action and toxicity. The present findings about the compound are critically analyzed and its prospect as a lead molecule for drug discovery is highlighted. The databases employed for data collection are mainly through Google Scholar, PubMed, Scopus and Science Direct. In-vitro and in-vivo studies showed that sinensetin possessed strong anticancer activities and a wide range of pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, anti-obesity, anti-dementia and vasorelaxant activities. The studies provided some insights on its several mechanisms of action in cancer and other disease states. However, more detail mechanistic studies are needed to understand its pharmacological effects. More in vivo studies in various animal models including toxicity, pharmacokinetic, pharmacodynamic and bioavailability studies are required to assess its efficacy and safety before submission to clinical studies. In this review, an insight on sinensetin pharmacological activities and mechanisms of action serves as a useful resource for a more thorough and comprehensive understanding of sinensetin as a potential lead candidate for drug discovery.

The COVID-19 pandemic and the lockdown measures have taken a toll on every level of the society, worldwide. This study examines their psychological impact on university students in Asia. A cross-sectional online survey was conducted between April and May 2020 in Malaysia, Saudi Arabia, Pakistan, Bangladesh, China, India and Indonesia. The Zung's self-rating anxiety scale (SAS) and questions on adaptive and maladaptive coping strategies were used in this study. A total of 3,679 students from the seven countries participated in this study. Overall, 21.9% and 13.7% of the students in this study experienced mild to moderate and severe to extreme levels of anxiety. More than 20% of the students from China and Bangladesh reported severe to extreme level of anxiety compared to below 10% of the students from Indonesia, Malaysia and India. Among the female students, 15.9% experienced severe to extreme level of anxiety compared to 10.6% among the males. Females from Bangladesh, China, Malaysia, Pakistan and Saudi Arabia experienced significantly higher levels of anxiety compared to their male counterparts. Acceptance was the most used and Seeking Social Support was the least used coping strategies among the students. There were significant differences in the usage of the four strategies by countries. Stressors are predominantly financial constraints, remote online learning, and uncertainty related to their academic performance, and future career prospects.

Leukemia is the most common type of hematological malignancies. Several natural products including bioactive peptides have been explored and studied for their anti-leukemic activities. In the present study, anti-leukemic peptide, IGTLILM (IM-7), was isolated and identified from the protein hydrolysate of sesame seeds by reverse phase-solid phase extraction, off-gel fractionation and nano LC-MS/MS. The cytotoxic effects of IM-7 were studied in MOLT-4 and NB4 acute leukemic cell lines using an MTT assay. The induction of apoptosis and autophagy was investigated by flow cytometry using Annexin V-FITC/PI staining and anti-LC3/FITC antibodies, respectively. The mRNA alterations of apoptotic and autophagic-related genes were determined by reverse transcription-quantitative PCR. The present study found that IM-7 inhibited the proliferation of MOLT-4 and NB4 cells in dose-dependent manner, but it showed a minimal effect on healthy mononuclear cells. IM-7 activated apoptosis and autophagy through the upregulation of CASP3, ULK1 and BECN1 and the downregulation of BCL2. In addition, IM-7 enhanced the cytotoxic effect of the anti-leukemic drug, daunorubicin. The findings suggested that IM-7 was potent to suppress the proliferation of MOLT-4 and NB4 leukemic cells and induce apoptosis and autophagy through the regulation of caspase 3-Bcl-2 and ULK1-Beclin1, respectively. [ABSTRACT FROM AUTHOR]

SESN2 is a member of the evolutionarily conserved sestrin protein family found in most of the Metazoa species. The SESN2 gene is transcriptionally activated by many stress factors, including metabolic derangements, reactive oxygen species (ROS), and DNA-damage. As a result, SESN2 controls ROS accumulation, metabolism, and cell viability. The best-known function of SESN2 is the inhibition of the mechanistic target of rapamycin complex 1 kinase (mTORC1) that plays a central role in support of cell growth and suppression of autophagy. SESN2 inhibits mTORC1 activity through interaction with the GATOR2 protein complex preventing an inhibitory effect of GATOR2 on the GATOR1 protein complex. GATOR1 stimulates GTPase activity of the RagA/B small GTPase, the component of RagA/B:RagC/D complex, preventing mTORC1 translocation to the lysosomes and its activation by the small GTPase Rheb. Despite the well-established role of SESN2 in mTORC1 inhibition, other SESN2 activities are not well-characterized. We recently showed that SESN2 could control mitochondrial function and cell death via mTORC1-independent mechanisms, and these activities might be explained by direct effects of SESN2 on mitochondria. In this work, we examined mitochondrial localization of SESN2 and demonstrated that SESN2 is located on mitochondria and can be directly involved in the regulation of mitochondrial functions.

SESN2 is a member of the evolutionarily conserved sestrin protein family found in most of the Metazoa species. The SESN2 gene is transcriptionally activated by many stress factors, including metabolic derangements, reactive oxygen species (ROS), and DNA-damage. As a result, SESN2 controls ROS accumulation, metabolism, and cell viability. The best-known function of SESN2 is the inhibition of the mechanistic target of rapamycin complex 1 kinase (mTORC1) that plays a central role in support of cell growth and suppression of autophagy. SESN2 inhibits mTORC1 activity through interaction with the GATOR2 protein complex preventing an inhibitory effect of GATOR2 on the GATOR1 protein complex. GATOR1 stimulates GTPase activity of the RagA/B small GTPase, the component of RagA/B:RagC/D complex, preventing mTORC1 translocation to the lysosomes and its activation by the small GTPase Rheb. Despite the well-established role of SESN2 in mTORC1 inhibition, other SESN2 activities are not well-characterized. We recently showed that SESN2 could control mitochondrial function and cell death via mTORC1-independent mechanisms, and these activities might be explained by direct effects of SESN2 on mitochondria. In this work, we examined mitochondrial localization of SESN2 and demonstrated that SESN2 is located on mitochondria and can be directly involved in the regulation of mitochondrial functions. [ABSTRACT FROM AUTHOR]

6-gingerol is a traditional medicine that possesses anti-cancer activity against several types of cancer. However, the mechanism of action still remains unclear. Therefore, this study explored the effects of 6-gingerol on antileukemic mechanisms in NB4, MOLT4, and Raji leukemic cell. Results indicated that 6-gingerol inhibited cell proliferation and induced cell apoptosis in these 3 cell lines. Moreover, 6-gingerol was shown to increase the mRNA expression of the caspase family thereby suggesting that 6-gingerol induced apoptosis through the caspase-dependent pathway. To explore the signaling pathway regulating 6-gingerol induced apoptosis, we utilized and integrated the network pharmacology approach together with experimental investigations. Targets of 6-gingerol were identified from ChEMBL and STITCH databases, which were used for constructing the protein-protein interaction (PPI) network. Results from the PPI network indicated that p53 was a key regulator. Moreover, it was found that 6-gingerol could increase the levels of p53 mRNA in all leukemic cell lines. Thus, 6-gingerol has shown to have anti-cancer activity. In addition, p53, BAX and BCL2 could be involved in the apoptosis pathway of these leukemic cells. This study is anticipated to be useful for the development of 6-gingerol as an anti-leukemic drug in the future. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms that regulate cancer progression is pivotal for the development of new therapies. Although p53 is mutated in half of human cancers, its family member p73 is not. At the same time, isoforms of p73 are often overexpressed in cancers and p73 can overtake many p53 functions to kill abnormal cells. According to the latest studies, while p73 represses epithelial–mesenchymal transition and metastasis, it can also promote tumour growth by modulating crosstalk between cancer and immune cells in the tumor microenvironment, M2 macrophage polarisation, Th2 T-cell differentiation, and angiogenesis. Thus, p73 likely plays a dual role as a tumor suppressor by regulating apoptosis in response to genotoxic stress or as an oncoprotein by promoting the immunosuppressive environment and immune cell differentiation.

The degradation of most intracellular proteins is a dynamic and tightly regulated process performed by proteasomes. To date, different forms of proteasomes have been identified. Currently the role of non-constitutive proteasomes (immunoproteasomes (iPs) and intermediate proteasomes (intPs)) has attracted special attention. Here, using a CRISPR-Cas9 nickase technology, four cell lines: histiocytic lymphoma, colorectal adenocarcinoma, cervix adenocarcinoma, and hepatocarcinoma were modified to express proteasomes with mCherry-tagged β5i subunit, which is a catalytic subunit of iPs and intPs. Importantly, the expression of the chimeric gene in modified cells is under the control of endogenous regulatory mechanisms and is increased following IFN-γ and/or TNF-α stimulation. Fluorescent proteasomes retain catalytic activity and are distributed within the nucleus and cytoplasm. RNAseq reveals marginal differences in gene expression profiles between the modified and wild-type cell lines. Predominant metabolic pathways and patterns of expressed receptors were identified for each cell line. Using established cell lines, we demonstrated that anti-cancer drugs Ruxolitinib, Vincristine and Gefitinib stimulated the expression of β5i-containing proteasomes, which might affect disease prognosis. Taken together, obtained cell lines can be used as a platform for real-time studies of immunoproteasome gene expression, localization of iPs and intPs, interaction of non-constitutive proteasomes with other proteins, proteasome trafficking and many other aspects of proteasome biology in living cells. Moreover, the established platform might be especially useful for fast and large-scale experiments intended to evaluate the effects of different conditions including treatment with various drugs and compounds on the proteasome pool.

Objective: The purpose of this investigation was to compare the repeatability of an intraoral scanner (3Shape TRIOS) with the traditional visual method for dental shade matching in patients and to assess the influence of ambient lighting and the observer's sex and experience on visual shade matching. An additional aim was to determine the color dimension for which repeatability is greater with both the visual method and intraoral scanner. Methods: Thirty observers (15 men and 15 women), grouped by professional experience, selected the shade of the right maxillary central incisor in 10 patients on three different occasions under different ambient lighting conditions (twice under studio clinic lighting and once under natural light). The same procedure was repeated using an intraoral scanner. All shades were selected based on the VITA Toothguide 3D-MASTER. The repeatability of each observer and the intraoral scanner were recorded for each color dimension (hue, chroma, and value). Results: The TRIOS intraoral scanner obtained a mean repeatability of 86.66% in dental shade matching compared to 75.22% achieved by the visual method. Ambient lighting had a direct effect on the repeatability of the shade selection for the visual method, whereas the observer's sex and clinical experience did not. For the visual method, the repeatability in dental shade matching depended on the dimension studied, with the best results in value, followed by hue and chroma; however, such dependence was not detected for the intraoral scanner. Conclusions: The TRIOS intraoral scanner ensured better repeatability than the visual method in dental shade matching.

Oil weathering models are essential for predicting the behavior of spilled oil in the environment. Most models use a "Pseudo Component" (PC) approach to represent the wide range of compounds found in petroleum products. Within the approach, rather than modeling each individual compound in an oil, a manageable number of PCs are developed that represent whole classes of compounds. However, previous studies focused mainly on traditional crude oils and did not develop a generic approach to create an optimal set of PCs for a variety of oils. In developing the updates to the NOAA oil weathering model, we propose herein a generic approach to construct PCs using oil distillation data to capture the complexity of oil evaporative weathering. We validated our approach with 899 oils from the Automated Data Inquiry for Oil Spills (ADIOS) oil library and found that an optimal set of sixteen PCs should be used. These PCs include two with low boiling point (below 144 °C), one with a high boiling point (above 400 °C), and thirteen constructed within a middle range of boiling points with a temperature resolution of 20 °C. Our simulation tests suggested that this set of sixteen PCs adequately characterizes oil evaporation processes for a wide variety of oils. [Display omitted] • A pseudo-component approach is developed for modeling oil evaporative weathering. • 16 pseudo-components constructed to model oil evaporation are tested with 899 oils. • Empirical formulas are derived to estimate pseudo-components' density and viscosity. [ABSTRACT FROM AUTHOR]

Following the 2010 Deepwater Horizon accident of a massive blow-out in the Gulf of Mexico, scientists from government, industry, and academia collaborated to advance oil spill modeling and share best practices in model algorithms, parameterizations, and application protocols. This synergy was greatly enhanced by research funded under the Gulf of Mexico Research Initiative (GoMRI), a 10-year enterprise that allowed unprecedented collection of observations and data products, novel experiments, and international collaborations that focused on the Gulf of Mexico, but resulted in the generation of scientific findings and tools of broader value. Operational oil spill modeling greatly benefited from research during the GoMRI decade. This paper provides a comprehensive synthesis of the related scientific advances, remaining challenges, and future outlook. Two main modeling components are discussed: Ocean circulation and oil spill models, to provide details on all attributes that contribute to the success and limitations of the integrated oil spill forecasts. These forecasts are discussed in tandem with uncertainty factors and methods to mitigate them. The paper focuses on operational aspects of oil spill modeling and forecasting, including examples of international operational center practices, observational needs, communication protocols, and promising new methodologies.

Objective: Thalassemia is one of the genetic diseases that cause anemia and ineffective erythropoiesis. Increased levels of several inflammatory cytokines have been reported in β thalassemia and might contribute to ineffective erythropoiesis. However, the mechanism by which tumor necrosis factor-alpha (TNF-α) is involved in ineffective erythropoiesis in thalassemic patients remains unclear. The objective of this study is to investigate the effect of TNF-α on the erythropoietin (EPO) and erythropoietin receptor (EPOR) expression involved in proliferation of β-thalassemia/hemoglobin (Hb) E erythroid progenitor cells compared with cells from healthy subjects. Materials and Methods: CD34-positive cells were isolated from heparinized blood by using the EasySep® CD34 selection kit. Cells were then cultured with suitable culture medium in various concentrations of EPO for 14 days. The effect of TNF-α on percent cell viability was analyzed by trypan blue staining. In addition, the percentage of apoptosis and levels of EPOR protein were measured by flow cytometry. Results: Upon EPO treatment, a higher cell number was observed for erythroid progenitor cells from both healthy participants and β-thalassemia/Hb E patients. However, a reduction of apoptosis was found in EPO-treated cells especially for β-thalassemia/ Hb E patients. Interestingly, TNF-α caused higher levels of cell apoptosis and lower levels of EPOR protein in thalassemic erythroid progenitor cells. Conclusion: TNF-α caused a reduction in the level of EPOR protein and EPO-induced erythroid progenitor cell proliferation. It is possible that TNF-α could be involved in the mechanism of ineffective erythropoiesis in β-thalassemia/Hb E patients.

In this study, the electric field signatures of negative ground flashes pertinent to the Swedish thunderstorms were recorded simultaneously during the summer of 2014 using wide (up to 100 MHz) and narrow (at 3 MHz and 30 MHz as central frequencies) bandwidth antenna systems. The electric field signatures were recorded for a time duration of 250 ms. In the analysis, the whole flash was considered and a total of 98 flashes were chosen where electric field signatures of all wideband, 3 MHz and 30 MHz signals were present. It is observed that preliminary breakdown pulses are stronger radiators at 3 and 30 MHz compared to the return strokes. A comparison of our results with those of the previous studies obtained from different geographical regions clearly shows that the strength of preliminary breakdown pulses is higher in the temperate region (Sweden for instance) and is a function of latitude.

This study attempted to explore the mechanisms involved in pinostrobin (PN)-mediated acute leukemia cell apoptosis regulated by miR-410-5p. NB4 and MOLT-4 cells were cultured and treated with PN at the IC50 concentration. Apoptosis was examined by Annexin V-FITC/PI staining. RT–qPCR was used to measure the expression of caspase-3, BAK, BCL-W, and MCL-1. The target protein of PN was identified using LC–MS/MS followed by bioinformatic analysis. TargetScan, DIANA, and miRDB were used for the prediction of miRNAs involved in the PN-induced apoptosis mechanism. miRNA mimic transfection, RT–qPCR, and western blot analysis were performed to evaluate the regulatory effect of miRNA on its target and the involvement of miRNA in apoptosis induction by PN. In addition, the synergistic effect of PN and daunorubicin (DNR) were investigated by using the MTT assay. The results showed that PN reduced cell viability and induced apoptosis in both leukemia cell lines. From the LC–MS/MS and bioinformatics analysis, SFRP5 and miR-410-5p were selected as a potential PN target protein and miRNA, respectively. After miRNA mimic transfection, miR-410-5p, which is an onco-miRNA, was decreased and led to increased apoptosis in both cell lines, indicating that this miRNA is involved in PN-mediated apoptosis mechanisms. Moreover, PN demonstrated a synergistic effect with DNR, suggesting that PN may be used in combination with conventional chemotherapy drugs. PN regulates the expression of miR-410-5p and SFRP5 to promote apoptosis in acute leukemia cells. It could be developed as an alternative treatment for leukemia in the future. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are currently intensively studied due to significant promise which they represent for successful implementations of future cell therapy clinical protocols. This in turn emphasizes importance of careful preclinical studies of MSC effects in various murine disease models. The appropriate cell preparations with reproducible biological properties are important to minimize variability of results of experimental cell therapies. We describe here a simple protocol for isolation of murine MSCs from adipose tissues and their reproducible multi-log expansion under hypoxia conditions.

The concept of Clusters seems to belong to the present whereas actually it is an old economic concept. Even classics (e.g. David Ricardo) or old neoclassic (e.g. Alfred Marshall) have still significant references for the today, whereas present produced enough favorable environment for. This paper will develop some of all references about, economic thinking, description and policy issues to be noted on. Moreover, the new need of clusters consists in the scenery that the economy exposes and preserves today. Risks, disadvantages and all that shadow such new current character and actor‟ are not only inherent, but keep their place in context. The specific cluster policy, in its turn, explicitly identifies what the national level‟s interests and the barriers of achieving those goals are and how cluster approach can help overcome these problems. It equally weights the relative merits of active intervention from the national level, versus framework conditions and facilitation, vis-à-vis theories and models.

O presente artigo buscou, através de um estudo interdisciplinar, envolvendo geografia, história e a teoria das representações sociais, identificar o patrimônio cultural do Distrito do Saí, em São Francisco do Sul/SC, e assim relacionar o potencial turístico da região com a preservação dos bens locais. Foram aplicados 300 questionários e realizadas 18 entrevistas orais com a população do município para a identificação e a análise dessas representações sociais. A partir disso, foram selecionadas 23 unidades patrimoniais de relevante interesse cultural, as quais foram registradas e mapeadas. A pesquisa resultou na confecção de um acervo cartográfico georreferenciado com a identificação dessas unidades, podendo ser utilizado em qualquer ambiente SIG. O resultado da pesquisa poderá ser utilizado como subsídio à criação de novas ferramentas de gestão as quais tenham como objetivo a preservação do patrimônio, bem como possibilitem com que a população tenha acesso a esses locais, tendo em vista seu potencial turístico e sua importância histórica.

In this study, electromagnetic field radiation bursts known as chaotic pulse trains (CPTs) and regular pulse trains (RPTs) generated by lightning flashes were analyzed. Through a numerical analysis it was found that a typical CPT could be generated by superimposing several RPTs onto each other. It is suggested that the chaotic pulse trains are created by a superposition of several regular pulse trains. Since regular pulse trains are probably created by dart or dart-stepped leaders or K-changes inside the cloud, chaotic pulse trains are caused by the superposition of electric fields caused by more than one of these leaders or K-changes propagating simultaneously. The hypothesis is supported by the fact that one can find regular pulse trains either in the beginning, middle or later stages of chaotic pulse trains.

Oil spills have been recognized as among the worst kinds of environmental disasters, causing severe coastal ecological and economic damages. Although benthic flow and solute fluxes are known to have strong impacts on fate and transport of oil deposited within marine sediments, their endogenous mechanisms still remain to be uncovered. In this paper, simulations of flow and solute transport processes along with hydrocarbon biodegradation were conducted in a cylindrical benthic chamber system to investigate influences of benthic hydrodynamics on oil biodegradation in permeable marine sediments. Results show that ripple-flow interactions create subsurface recirculation cells whereby seawater infiltrates into the benthic sediments at ripple troughs while groundwater discharges near the crests. It results in a spatially varied oil biodegradation rate in marine sediments. Significant oil biodegradation occurs near sediment ripple troughs due to direct oxygen recharge, while biodegradation of oil deposited uphill becomes slow due to limited oxygen replenishment. Oil biodegradation decreases subsurface oxygen content, and consequently impedes discharge of oxygen from benthic sediments. Our results reveal a dynamic interaction between oil biodegradation and benthic flow and solute transport processes, which has strong implications for predicting oil persistence and biodegradation within marine sediments and its associated impacts on benthic biogeochemical processes. [Display omitted] • Ripple-flow interactions cause benthic spatially varied oil biodegradation rate. • Benthic oil biodegradation primarily depends on local topographic and flow patterns. • Oil biodegradation primarily occurs in ripple troughs due to direct oxygen recharge. • Biodegradation of benthic oil deposited uphill is slow due to anaerobic conditions. [ABSTRACT FROM AUTHOR]

This paper presents the characteristics of the preliminary breakdown pulses (PBP) in 51 positive ground flashes recorded during 2014 summer thunderstorms in Sweden. Electric field measurements were conducted remotely using a broadband antenna system (up to 100 MHz) for a recording length of 1 s with 200 ms trigger time. In the analysis, PBP trains were observed in 86% of the cases. Based on the number of trains preceding the first return stroke, the PBP were classified into single and multiple train PBP. Characteristics of the first PBP train were determined and based on the initial polarity of the pulses, three types of PBP were identified. Characteristics of the subsequent PBP trains in the multiple train PBP were also analyzed and they were compared with the first PBP train. Based on the conceptual charge cloud configuration, we found that the inverted dipole is consistent with our observation. We also found that PBP in positive ground flashes during summer thunderstorms in Sweden are weak since the average ratios of the PBP peak to the first return stroke peak lie only between 0.21 and 0.26. Possible reasons for no detection of PBP and the different types of PBP observed were also discussed.

Recently, some cytokines were used as immunotherapy for leukemic patients, which improved cancer therapy by apoptosis induction. This study investigated the effects of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) on induction of cell apoptosis in leukemic cell lines, K562 and HL60. Both of leukemic cell lines were treated with IL-1β and TNF-α in various concentrations and incubation times. Cell viability and growth inhibition were analyzed by using trypan blue staining and MTT assay, respectively. Apoptotic cells were stained with Annexin-V-FITC and analyzed by flow cytometry. In addition, the involvement of caspase activation in the apoptotic pathway was investigated. The results indicated that percentage of cell viability was decreased while cell apoptosis increased after treatment with 2 ng/ml IL-1β or 20 ng/ml TNF-α in both leukemic cell lines. The increased sub G1 population from cell cycle analysis and cell morphology indicated increasing apoptosis in cytokines treated cells. Caspase 3 and caspase 8 activity were increased after IL-1β and TNF-α treatment. These results suggest that IL-1β and TNF-α could induce apoptosis via caspase cascade pathway in K562 and HL60 cell lines. [ABSTRACT FROM AUTHOR]

In this study we intend to provide an overview on fossilized tree resins (amber) commonly found in Southeast Asia, more particularly in the Indo-Australian Archipelago (IAA). These remains are often referred in literature as "Indonesian amber", "Borneo amber" or simply as "dammar". They are very common in the region and the Brunei Sultanate is no exception as most of its Neogene sedimentary successions contain amber-rich layers. Although amber is a common fossil in the country and in northern Borneo, to our knowledge it has not been studied in great detail so far. Here we present an account on the "Borneo Ambers" from Brunei, regarding their stratigraphic origin, basic physical properties, their interaction with the biosphere and their botanical origin using Fourier-transform infrared spectroscopy (FTIR). Additionally, a number of ambers and modern tree resins were analysed for their carbon isotope composition and a few were tested with gas chromatography. We discuss the results in a regional and global context, in comparison with available data from the IAA. The ambers come from four different lithostratigraphic units with an age range of 12 to 3 million years (middle Miocene to Pliocene). Recently reworked ambers from the coast, ambers from younger alluvial deposits, and several modern tree resins from Dipterocarpaceae and Araucariaceae (Agathis borneensis) were also included in the study. The >60 FTIR analyses of modern and fossil specimens suggest that all the Brunei ambers were produced by trees of Dipterocarpaceae. There is no indication of Agathis in the fossil record, in agreement with their lower abundance in the forests of Borneo. Modern and fossil dipterocarp resins were found to be different based on the following criteria: (1) Different reactions to solubility, hot needle and UV tests with faster reaction time and less fluorescence for the modern ones; (2) Clear distinction based on certain FTIR absorbance band ratios, mostly by those that represent carboxylic acids and esters (e.g., ~1700 and 1243 cm-1); (3) Modern resin yielded on an average 3‰ lower δ13C values, (4) Gas chromatography data reflect maturation differences among the samples. Although there is some overlap in the chemical results between the two groups, generally all these differences reflect different maturation stages of the resinous material and point towards loss of low δ13C components from the organic structure of the resin. The minor timewise decreasing trend in average δ13C from the late middle Miocene to late Miocene can be explained by (1) gradual changes in local environmental conditions, and/or (2) increased amount of less mature specimens among the younger samples. In contrast, the highest obtained δ13C values were found in the youngest Pliocene ambers. Instead of maturation bias this can be linked to environmental factors such as cooler-drier climate with increased seasonality, probably reflecting the onset of the northern hemisphere glaciation. [ABSTRACT FROM AUTHOR]

Fucoxanthin, as a main marine carotenoid, exhibit a wide variety of bioactivities, including antioxidant activity. Previously, we have shown the geroprotective activity of fucoxanthin on Drosophila and C. elegans. Our new study aimed to compare the antioxidant activity of fucoxanthin in early and late passage normal human cells LECh4(81) in physiological conditions and under oxidative stress. In addition, using the RNA-seq we have analyzed the transcriptomic changes during the replicative senescence of fibroblasts treated with fucoxanthin. Results showed that fucoxanthin at a concentration of 5 μM caused the most pronounced antioxidant effect in the late passage cells. Moreover, transcriptomic data showed the increased expression levels of genes related to the Nrf2/ARE pathway. According to the analysis of enriched KEGG pathways, fucoxanthin altered cellular processes like ribosome biogenesis, lipid metabolism, and cell cycle regulation including some age-related pathways such as Wnt, JAK-STAT, and FoxO signaling pathways. We suggest that fucoxanthin may have therapeutic potential for treating age-related diseases., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

SESTRINs (SESN1-3) are proteins encoded by an evolutionarily conserved gene family that plays an important role in the regulation of cell viability and metabolism in response to stress. Many of the effects of SESTRINs are mediated by negative and positive regulation of mechanistic target of rapamycin kinase complexes 1 and 2 (mTORC1 and mTORC2), respectively, that are often deregulated in human cancers where they support cell growth, proliferation, and cell viability. Besides their effects on regulation of mTORC1/2, SESTRINs also control the accumulation of reactive oxygen species, cell death, and mitophagy. SESN1 and SESN2 are transcriptional targets of tumor suppressor protein p53 and may mediate tumor suppressor activities of p53. Therefore, we conducted studies based on a mouse lung cancer model and human lung adenocarcinoma A549 cells to evaluate the potential impact of SESN1 and SESN2 on lung carcinogenesis. While we observed that expression of SESN1 and SESN2 is often decreased in human tumors, inactivation of Sesn2 in mice positively regulates tumor growth through a mechanism associated with activation of AKT, while knockout of Sesn1 has no additional impact on carcinogenesis in Sesn2-deficient mice. However, inactivation of SESN1 and/or SESN2 in A549 cells accelerates cell proliferation and imparts resistance to cell death in response to glucose starvation. We propose that despite their contribution to early tumor growth, SESTRINs might suppress late stages of carcinogenesis through inhibition of cell proliferation or activation of cell death in conditions of nutrient deficiency., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

The anaesthetic hazards for the obstetric patient are well known. Based on results of the first two reports on the confidential enquiry into maternal deaths in Malaysia for 1991 and 1992, ten cases of anaesthetic related deaths were analysed. There were 3 in 1991 and 7 in 1992 accounting for 1.34% and 2.8% of maternal deaths respectively. It was estimated that the crude mortality rate for the obstetric patient was 11.4 per 100,000 operative deliveries or a four-fold risk compared to the general surgical patient. One case resulted from administration of intravenous sedation while the rest involved general anaesthesia, seven of which were done under emergency conditions. Inadequate airway management and ventilation in the perioperative period, including during interhospital transfer was the single most important factor causing the majority of these deaths. The use of regional anaesthesia for Caesarean sections is strongly advocated. Substandard care was also present in all cases. Other issues pertinent to improvement of obstetric anaesthetic services are also discussed which include the quality of anaesthetic manpower, upgrading of infrastructure, facilities and staffing of operating and recovery areas, the use of regional anaesthesia, expanding the role of the anaesthetist and the quality of the anaesthetic services in general.

To detect d-mannose-sensitive (MS) pili in 31 P. aeruginosa strains isolated from the respiratory tract of patients with inflammatory and purulent destructive pulmonary diseases, the hemagglutination (HA) test was used. The isolated Pseudomonas under study differed in the degree of manifestation of their MS adhesins. Among them microorganisms with pronounced HA activity (high HA titer) occurred, as well as those whose HA activity was less pronounced (low HA titer). P. aeruginosa strains with pronounced HA activity were more frequently isolated from patients with purulent destructive processes in the lungs. A correlation between the state of the patient at the moment of bacteriological examination and the degree of manifestation of MS pili in the P. aeruginosa strain isolated from this patients was established. The value of HA titer in the presence of d-mannose is indicative of the presence of MS adhesins in a P. aeruginosa strain.

In patients with toxic infections salmonellae were identified in 31% of cases. The patients were divided into two groups: the control group receiving treatment with infusion solutions and the test group treated, in addition to the usual scheme of therapy, with indomethacin in a daily dose of 150 mg. The study revealed that salmonellae isolated at the initial stages of the disease possessed highly pronounced adhesive properties. The adhesive properties of salmonellae isolated at the stage of convalescence from the patients of the test group were considerably less pronounced than those of salmonellae isolated from the same patients at the peak of the disease. In the control group no differences in the adhesive properties of salmonellae isolated from the same patients were established.