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Aims: Lactate acid functions as not only an energy source but a signaling molecule through the lactate receptor GPR81 under physiological conditions. However, the pathological role of lactic acid in the tumor microenvironment remains unclear, particularly for immune cells. Methodology: NK-92 cells were treated with L-lactic acid solutions at final concentrations of 10, 20, 30, and 40 mM, and its cell viability and cytotoxicity on A549 cells and A375 cells were evaluated by CCK8 assay and crystal violet assay, respectively. Furthermore, qPCR was used to assess the expression of GPR81 and cytotoxicity-related genes in NK-92 cells treated with antagonist and agonist. And their relationship between lactate/GPR81 pathway and cytotoxicity-related genes were analyzed by Pearson’s correlation. Results: The viability of NK-92 cells was inhibited by L-lactic acid with increasing concentration. Additionally, the cytotoxic activity against tumor cells of NK-92 cells treated with L-lactic acid decreased with increasing concentration. Moreover, qPCR results demonstrated that GPR81 can be activated by lactic acid or agonist (3,5-DHBA) and downregulate the expression cytotoxicity-related genes which included FASLG gene(Fas Ligand),TNF-? gene(Tumor necrosis factor-?), INFG gene (Interferon-?), RPF1 gene (Perforin 1), GZMA gene (Granzyme A), GZMB gene (Granzyme B), GZMH gene (Granzyme H), GAMK gene (Granzyme K) and GZMM gene (Granzyme M). And the expression of GPR81 returned to near-control level when treated with L-lactic acid in the presence of antagonist (3-OBA), the expression of cytotoxicity-related genes did as well. Pearson’s correlation analysis of cytotoxicity-related genes with GPR81 revealed that their correlation coefficient seems negative. Conclusion: Lactic acid can activate the GPR81 to downregulate the expression of cytotoxicity-related genes, subsequently lower the cytotoxicity of NK-92 cells.
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@#This study aims to examine the efficacy of mosquito mat vaporizers on Aedes aegypti and their associated metabolic detoxication mechanisms. For this purpose, Aedes aegypti (Linnaeus) was collected from nine districts in Selangor, Malaysia and tested with mosquito vaporizing mat bioassays. The same populations were also subjected to biochemical assays to investigate activities of detoxifying enzymes, namely non-specific esterase (EST), glutathione-S-transferase (GST) and mixed function oxidase (MFO). The efficacy of Ae. aegypti on the active ingredients tested in decreasing order were d- allethrin > dimefluthrin > prallethrin with PBO > prallethrin. The results further indicated significant enhancement mean levels of EST, GST and MFO in pyrethroid-resistant populations. The mortality rate of Ae. aegypti in response to pyrethroid active ingredients was associated with MFO activity, suggesting it is an important detoxification enzyme for the populations tested. In view of the presence of resistance against household insecticide products, pyrethroid efficacy on Ae. aegypti populations needs to be monitored closely to ensure the implementation of an effective vector control program in Malaysia.
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@# Susceptibility status of Aedes albopictus (Skuse) sampled from residential areas in Interior, Sandakan and Tawau divisions of Sabah, Malaysia, was evaluated based on the WHOrecommended doses of organochlorine and organophosphate larvicides. To determine susceptibility status, larval bioassays were carried out and post 24-hour mortalities based on WHO resistance classifications were adopted. The results demonstrated that Ae. albopictus larvae were resistant toward 5 out of the 8 larvicides tested. Larvae from all populations were resistant against bromophos, fenitrothion, malathion, temephos and dichlorodiphenyltrichloroethane (DDT), with mortalities ranging from 0.00 to 89.33%. Dieldrin, on the other hand, could induce 100.00% mortalities in all populations, followed by fenthion and chlorpyrifos, with mortalities ranging from 97.33 to 100.00% and 81.33 to 100.00% respectively. Despite most populations exhibiting similitude in their resistance status, larvae from Sandakan exhibited the highest resistance level whereas the lowest level was observed in Keningau. In view of the inadequacy of some larvicides in controlling Ae. albopictus in this study, integrated management such as insecticide rotation or combination of interventions is warranted.
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This study was designed to evaluate the extent of the protection for bovine viral diarrhea virus type 2 (BVDV-2) infection, afforded by vaccination with a combo inactivated vaccine, which contains bovine viral diarrhea virus type 1 (BVDV-1) and infectious bovine rhinotracheitis virus (IBRV). Five 3-4-month-old calves were intramuscularly vaccinated with a single dose of the combo vaccine and boosted with same dose three weeks after the first vaccination, with five mock immunized calves serving as a control group. Twenty-one days after the second vaccination, all calves were challenged with BVDV-2 SX08 strain by spray into nostril. The unvaccinated animals developed typical clinical signs of high rectal temperature, diarrhoea with erosions and a dramatic drop in leukocyte counts. These signs occured markedly less in all vaccinated animals, the rectal temperature, leukopenia and virarmia of which, were significantly less than the mock immunized calves. It can be concluded that vaccination with the combo inactivated vaccine affords cross-protection against clinical effects of a challenge-infection with BVDV-2 SX08 strain, although it was part protection.(AU)
Este estudo foi desenvolvido para avaliar a extensão da proteção contra a infecção pelo vírus da diarréia viral bovina tipo 2 (BVDV-2) através da vacinação com uma vacina combinada inativada contendo o vírus da diarréia viral bovina tipo 1 (BVDV-1) e vírus da rinotraqueíte de bovinos infecciosos (IBRV). Cinco bezerros com 3 a 4 meses de idade foram vacinados via intramuscular com uma dose única da vacina combinada e reforçados com a mesma dose três semanas após a primeira vacinação, com cinco bezerros imunizados em simulação servindo como grupo controle. Vinte e um dias após a segunda vacinação, todos os bezerros foram desafiados com a cepa BVDV-2 SX08 por spray na narina. Os animais não vacinados desenvolveram sinais clínicos típicos, como alta temperatura retal, diarréia com erosões e queda drástica na contagem de leucócitos. Estes sinais tiveram ocorrência significativamente menor em todos os animais vacinados, cuja temperatura retal, leucopenia e virarmia eram significativamente menores do que os bezerros simulados. É possível concluir que a vacinação com a vacina combinada inativada proporciona proteção cruzada contra os efeitos clínicos de uma infecção provocada pela cepa BVDV-2 SX08, embora tenha sido parcialmente protegida.(AU)
Subject(s)
Animals , Cattle , Vaccination , Vaccines, Combined/analysis , Diarrhea Virus 1, Bovine Viral/immunology , Diarrhea Virus 2, Bovine Viral/immunology , Cross Protection , Vaccines, Inactivated , Leukocyte CountABSTRACT
@#Simulium (Simulium) contractum Takaoka from Sulawesi, Indonesia was known only as the pupa. Its female, male and mature larva are described for the first time. The tentative assignment of this species in the Simulium dumogaense species-group is confirmed by the adult characters including the female and male genitalia. The female and male of this species are similar to those of Simulium (Simulium) tumpaense Takaoka & Roberts but are distinguished by the yellowish femora.
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@#Some filarial nematodes, such as Wuchereria bancrofti, Brugia malayi, and Brugia timori, cause lymphatic diseases in humans in the tropics, whereas other filarial parasites from wild animals cause zoonotic diseases in humans worldwide. To elucidate the prevalence and diversity of filarial parasites in Malaysia, we investigated the filarial parasites from wild animals in Gemas, Negeri Sembilan. To find adult filarial parasites, we dissected 26 animals, which included five frogs, one skink, one snake, two birds, six common treeshrews, and 11 rats. Then, we examined microfilariae in the blood smears and skin snips obtained from each animal. We found two types of microfilariae in the blood smears of common treeshrews: one was very similar to Malayfilaria sofiani and the other closely resembled Brugia tupaiae. These findings indicate an additional distribution of these filarial parasites in Gemas.
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Context: C-Cbl is an important negative regulator of the cell signaling that acts as an adaptor protein and E3 ubiquitin ligase. The role of c-Cbl in development and regulation of human cancer has aroused intensive attention. Aims: In this study, we aimed to assess the correlation between the expression of c-Cbl and clinicopathological parameters and explored the role of c-Cbl in the development and progression of GC. Settings and Design: This is a Pilot study. Methods and Materials: In total, 84 tissue samples including 44 gastric cancers (GC) and 40 matched adjacent normal tissues were collected after surgery. Then tissue microarray (TMA) and immunohistochemistry (IHC) technology were combined to detect the protein expression of c-Cbl. Statistical Analysis Used: Statistical analysis was performed using SPSS 22.0 (IBM Corporation, Armonk, NY, USA). Results: We have studied the correlation between c-Cbl expression and clinicopathological parameters. Our study showed that c-Cbl has a low expression in 61.4% (27/44) of GC tissues, and the incidence of cases was significantly higher than that in adjacent normal tissues (P < 0.0001). In addition, the correlation between c-Cbl expression and gastric carcinoma subtype (P = 0.027), histological type (P = 0.033), Borrmann classification (P = 0.009), histological differentiation (P = 0.0005), lymph node metastasis (P = 0.007), and intravascular tumor thrombus (P = 0.036) has also been revealed. Conclusions: Our results show that c-Cbl is down-regulated in GC tissues compared with normal gastric tissue, which may play an important role in the development and progression of GC.
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Objective: To examine the psychometric properties of the Chinese version of the Yale-Brown Obsessive Compulsive Scale - Second Edition (Y-BOCS-II). Method: A total of 86 adults with a primary diagnosis of obsessive-compulsive disorder (OCD), ranging in age from 15 to 78 years, participated in the study. Participants were administered the Y-BOCS-II by a trained clinician who also rated overall illness severity on two additional measures. Patients completed the Obsessive Compulsive Inventory-Revised and Depression Anxiety Stress Scale-21. Results: Results indicated high internal consistency and fair 1-week test retest reliability. The Y-BOCS-II scales correlated strongly with clinician-rated obsessive-compulsive severity and modestly with self-reported obsessive-compulsive symptom frequency and distress. The relationship between Y-BOCS-II total score and depressive and anxiety symptoms was strong, which may reflect high rates of comorbid conditions in this sample or the linkage between obsessive-compulsive symptom severity and distress. Factor analysis demonstrated a two-factor structure consisting of obsession and compulsion factors, with interference due to obsessions cross-loading. Conclusions: Overall, these results support the use of the Y-BOCS-II among individuals from China. Future study by an independent group is necessary to replicate these findings, as well as investigate interrater reliability and treatment sensitivity.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Aged , Young Adult , Psychiatric Status Rating Scales/standards , Surveys and Questionnaires/standards , Obsessive-Compulsive Disorder/diagnosis , Psychometrics , Severity of Illness Index , China , Reproducibility of Results , Factor Analysis, Statistical , Language , Middle Aged , Obsessive-Compulsive Disorder/psychologyABSTRACT
@#A new black fly species, Simulium yukawai, is described on the basis of one female and its pupal exuviae from Vietnam. This new species is placed in the S. crocinum species-group of Simulium (Simulium) (Diptera: Simuliidae). It is characterized in the female by the paraproct covered with 48–50 distinct hairs on its ventral and lateral surfaces, and in the pupa by the frons and most of the thorax bare, gill with six dark filaments in three pairs closely arising from the base, of which the two outer filaments of the dorsal and middle pairs are much longer than other filaments, abdomen with distinct spine-combs on the dorsal surface of segments 7–9, and cocoon wall-pocket shaped, with a large anterolateral window on each side. Taxonomic notes are given to separate this new species from related species. This species is the fourth member of the S. crocinum species-group known from Vietnam.
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@#Ovitrap surveillance was conducted to determine the infestation patterns of dengue vectors in fourteen study sites across eight provinces located in the Sunda Islands, Indonesia. High ovitrap indices up to 70% and 90% were obtained from indoor and outdoor areas, respectively. Mean numbers of Ae. aegypti and Ae. albopictus larvae ranged from 0.13 to 14.50 and 0.10 to 18.60, respectively. Mixed infestation (<10%) and interchange of breeding habitat preferences of Ae. albopictus and Ae. aegypti were also observed in the present study.
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@#Simulium (Gomphostilbia) dhangi sp. nov., S. (G.) sumbaense sp. nov. and S. (Nevermannia) wayani sp. nov. are described from the Lesser Sunda Archipelago, Indonesia. Simulium (G.) sumbaense sp. nov. is placed in the S. varicorne species-group and is characterized by the pupal gill with eight filaments arranged as (1+1+1+1+2)+2 from dorsal to ventral, while S. (G.) dhangi sp. nov., unplaced to group, is characterized by the pupal gill composed of two inflated trunks and four slender filaments all arising basally, and the short larval antenna as long as the stem of the labral fan. Simulium (N.) wayani sp. nov. belongs to the S. ruficorne species-group and is characterized by the female spermatheca with an unsclerotized neck, and pupal gill with four inflated filaments. The number of species of black flies from the archipelago increases from 19 to 22.
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@#Ovitrap surveillance was carried out in fifteen localities encompassing foggingfree and dengue risk areas in West Malaysia to determine on the dispersal and prevalence of single and co-breeding of mosquito larvae particularly Aedes. Ovitraps were sited randomly indoors and outdoors within human settlements in all study areas. All the localities exhibited positive ovitraps with single breeding of Ae. albopictus that ranged between 64.29% and 100.00%. These findings indicated Ae. albopictus as the predominant container-breeding species in all study areas. The co-breeding of Ae. aegypti with Ae. albopictus larvae (34 ovitraps), Ae. albopictus with Culex quinquefasciatus larvae (32 ovitraps) as well as Cx. quinquefasciatus with Armigeres subalbatus larvae (1 ovitrap) were also detected in certain study localities. Interestingly, co-breeding of Ae. albopictus with Ar. subalbatus larvae as well as Ae. albopictus with Uranotaenia sp. larvae in Malaysia is reported for the first time in the present study. Better understanding of the co-breeding scenario involving different species of mosquito larvae is needed to ensure the efficacy of vector control actions to be conducted.
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Human-landing catch (HLC) technique was undertaken in nine selected study sites within Peninsular Malaysia to determine the biting cycle of Aedes, Armigeres, Culex, and Mansonia mosquitoes. HLC was conducted 24 hours on three different nights in a duration of one week at each study site. Aedes albopictus were found in all study sites with bimodal biting cycle, whereas the biting peak of Aedes butleri was recorded between 1600 and 1900 hr. For Armigeres, five study sites demonstrated similar biting peak hour (1900 – 2000 hr) for Ar. kesseli four study sites showed biting peak at 1800 – 1900 hr for Ar. subalbatus. Culex quinquefasciatus was collected from all study sites except in Sungai Penchala with its biting activity beginning from 1900 hr. Both Mansonia annulifera and Mansonia uniformis captured in two different study sites showed similar biting peaks (1500 – 1600 hr). It is recommended that vector control activities be carried out at dusk as almost all mosquito species captured started their biting activities at that time.
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This study aimed to explore the effects of continuous blood purification (CBP) treatment in pigs affected with acute respiratory distress syndrome (ARDS). A total of 12 healthy male pigs, weighing 12±1.8 kg, were randomly and equally assigned to the control and experimental groups. The ARDS pig model was prepared by intravenous injections of endotoxin (20 µg/kg). The control group was given conventional supportive therapy, while the experimental group was given continuous veno-venous hemofiltration therapy. During the treatment process, the variations in dynamic lung compliance, oxygenation index, hemodynamics, and urine volume per hour at different times (Baseline, 0, 2, 4, and 6 h) were recorded. The levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were measured using the enzyme-linked immunosorbent assay. The histomorphological changes of the lung, heart, and kidney were visualized using a light microscope. The nuclear factor κB p65 protein content of the heart, lung, and kidney tissues was also detected using western blot. The experimental group outperformed the control group in both respiratory and hemodynamic events. CBP treatment cleared TNF-α, IL-6, and IL-10 partially from serum and BALF. The pathological examination of the heart, lung, and kidney tissues revealed that the injury was less severe in the experimental group. CBP treatment can improve the organ functions of pigs affected with endotoxin-induced ARDS and protect these organs to some extent.
Subject(s)
Animals , Male , Hemofiltration/methods , Blood Gas Analysis , Disease Models, Animal , Endotoxins , Enzyme-Linked Immunosorbent Assay , Interleukin-10/analysis , Interleukin-6/analysis , Kidney/pathology , Lung/pathology , Myocardium/pathology , Random Allocation , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/therapy , Swine , Tumor Necrosis Factor-alpha/analysisABSTRACT
A preliminary survey of larvae and pupae of black flies (Diptera: Simuliidae) was conducted in three recreation parks [Templer Recreation Park (TRP), Congkak River Forest Reserve (CRFR) and Ampang Forest Reserve (AFR)] located in Selangor State, which is located 18 to 35 km from Kuala Lumpur city center, Malaysia. This study was initiated to determine the distribution and abundance of filarial vectors, Simulium spp. A total of 12 species of black flies belonging to three subgenera (Gomphostilbia, Simulium and Nevermannia) were collected. Simulium (Simulium) nobile was incriminated as the most dominant species in all recreation parks. This study is a first report on the distribution and abundance of black flies obtained from recreation parks in Malaysia.
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Lung cancer is the leading cause of cancer‑related mortality in the world, with more than 1 million deaths/year. Over the past years, lung cancer treatment has been based on cytotoxic agents and an improvement in the outcome and quality of life for patients has been observed. However, it has become clear that additional therapeutic strategies are urgently required to provide an improved survival benefit for patients. A major intracellular signaling pathway, the Hippo signaling pathways have been extensively studied in neoplasia, including lung cancer. Furthermore, the study of constitutively activated receptor and their downstream signaling mediators has become a promising new field of investigation for lung cancer treatment. Nevertheless for lung cancer, this approach has not been successful yet. Here, we will review the molecular basis of Hippo signaling in lung cancer and further discuss the therapeutic potential of multi‑targeted strategies involving Yes‑associated protein inhibitors.
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The growing body of evidence regarding the putative health benefits of green tea (Camellia sinensis), including reduced risk of cancer and cardiovascular disease, has led to an increase in the consumption of brewed green tea and the formulation of green tea extracts (GTE) into a variety of food and beverage products and food supplements. The principal bioactive ingredients in green tea beverages and GTE are polyphenols, particularly the flavan-3-ols, which have been shown to act on antioxidant, anti-inflammatory, glucoregulatory, and cell signaling pathways. Some experimental evidence and case reports suggest the use of green tea and GTE is associated with the potential for inducing liver injury. The ability to extrapolate findings from in vitro and animal model studies is always limited and the available results on green tea- and GTE-induced liver injury in humans have presented clinical and regulatory challenges due to the difficulty of demonstrating a causal relationship between intake and harm. Attention to the risk for hepatotoxicity has largely been focused on GTE. Existing data are insufficient to identify the causative agent in the preparation or composition of GTE or its dose or duration of use as well as nutrigenetic, medical, and other factors that may contribute to the risk of hepatotoxicity. Responses by different government regulatory agencies regarding the safety of GTE are inconsistent with one another, including the dosage and derivation of its bioactives from aqueous versus hydro-alcoholic extracts. Restrictions on the production of GTE limit the application of innovative extraction technologies that may improve the efficiency, quality, and cost-effectiveness of production and minimize the presence of endogenous or contaminant heavy metals as well as mycotoxins, pesticides, and other unwanted constituents. The objective of this review is to characterize the phytochemical profile of green tea and GTE, provide an updated description of the methods that could be used to extract green tea constituents, and discuss recent considerations on the potential for harm from consumption of GTE and products containing GTE.
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The residual activities of 5 insect growth regulators (IGRs) were studied and compared to operational dosage of temephos (1 mg/L) and Bacillus thuringiensis israelensis (Bti) (0.008 mg/L). The IGRs, temephos and Bti were applied into plastic containers containing 5 litres of water. Thirty Aedes aegypti larvae were added into each container weekly. Efficacy of these IGRs were evaluated for effective duration of each dosage and the percentage of emergence inhibition (EI). An end-point of EI/mortality > 50% was considered to be effective. Pyriproxyfen possessed the longest residual activity in both indoor (43 weeks) and outdoor (26 weeks) conditions, followed by temephos (26 weeks in indoor and 16 weeks in outdoor). Although the residual activity of Bti in indoor lasted 8 weeks which was longer than cyromazine and diflubenzuron; however, it was least effective in outdoor which only lasted 2 weeks. This study revealed that pyriproxyfen possessed good residual effect among test IGRs compared to temephos and Bti. The use of IGRs can be an alternative long-term control measure in stagnant water body.
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Given the lack of molecular evidence in altered target-site insecticide resistance mechanism in Aedes albopictus (Skuse) worldwide, the present study aims to detect the presence of A302S mutation in the gene encoding the gamma aminobutyric acid receptor resistant to dieldrin (Rdl) in Ae. albopictus for the first time from its native range of South East Asia, namely Malaysia. World Health Organization (WHO) adult susceptibility bioassay indicated a relatively low level of dieldrin resistance (two-fold) in Ae. albopictus from Petaling Jaya, Selangor. However, PCR-RFLP and direct sequencing methods revealed the presence of the A302S mutation with the predomination of heterozygous genotype (40 out of 82 individuals), followed by the resistant genotype with 11 individuals. This study represents the first fieldevolved instance of A302S mutation in Malaysian insect species.
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We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.