Burkholderia pseudomallei is a causative agent of melioidosis that can infect humans and animals in endemic countries,specifically in Southeast Asia and tropical Australia.A fundamental component for the pathogenesis ...Burkholderia pseudomallei is a causative agent of melioidosis that can infect humans and animals in endemic countries,specifically in Southeast Asia and tropical Australia.A fundamental component for the pathogenesis of Burkholderia pseudomallei is the capability of the bacterium to enter,survive,replicate,and cause disease in a host cell by inducing the host cell fusion.Cell fusion results in multinucleated-giant cell formation,thus enabling the dissemination of Burkholderia pseudomallei intracellularly.cGAS reacts to Burkholderia pseudomallei infection by activating the cGAS-STING pathway and subsequently limiting host's aberrant cell division and cellular replication by inducing autophagic cell death.In this review,we discuss the host-pathogen interactions between the typeⅥsecretion system 5(T6SS-5)of Burkholderia pseudomallei and human cGAS pathway in melioidosis infections.Since T6SS-5 is a main virulent factor in Burkholderia pseudomallei and the c GAS pathway is vital for host immune response,elucidating their functions is important for better understanding the pathogenesis of Burkholderia pseudomallei.展开更多
BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CR...BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.展开更多
Objective:To evaluate the prevalence of multidrug resistant Staphylococcus aureus(S.aureus) in dairy products.Methods:Isolation and identification of S.aureus were performed in 3 dairybased food products.The isolates ...Objective:To evaluate the prevalence of multidrug resistant Staphylococcus aureus(S.aureus) in dairy products.Methods:Isolation and identification of S.aureus were performed in 3 dairybased food products.The isolates were tested for their susceptibility to 5 different common antimicrobial drugs.Results:Of 50 samples examined,5(10%) were contaminated with 5. aureus.Subsequently,the 5 isolates were subjected to antimicrobial resistance pattern using five antibiotic discs(methicillin,vancomycin,kanamycin,chloramphenicol and tetracycline).Sample 29 showed resistance to methicillin and vancomycin.Sample 18 showed intermediate response to tetracycline.The other samples were susceptible to all the antibiotics tested.Conclusions:The results provide preliminary data on sources of food contamination which may act as vehicles for the transmission of antimicrobial-resistant Staphylococcus.Therefore,it enables us to develop preventive strategies to avoid the emergence of new strains of resistant S.aureus.展开更多
Objective:To assess antioxidant activities of different parts of Euphorbia hirta（E.hirta）,and to search for new sources of safe and inexpensive antioxidants.Methods:Samples of leaves,stems, flowers and roots from E....Objective:To assess antioxidant activities of different parts of Euphorbia hirta（E.hirta）,and to search for new sources of safe and inexpensive antioxidants.Methods:Samples of leaves,stems, flowers and roots from E.hirta were tested for total phenolic content,and flavonoids content and in vitro antioxidant activity by diphenyl-1-picrylhydrazyl（DPPH） assay and reducing power was measured using cyanoferrate method.Results:The leaves extract exhibited a maximum DPPH scavenging activity of（72.96±0.78）%followed by the flowers,roots and stems whose scavenging activities were（52.45±0.66）%,（48.59±0.97）%,and（44.42±0.94）%,respectively.The standard butylated hydroxytoluene（BHT） was（75.13±0.75）%.The IC<sub>50</sub>,for leaves,flowers,roots,stems and BHT were 0.803,0.972,0.989,1.358 and 0.794 mg/mL,respectively.The reducing power of the leaves extract was comparable with that of ascorbic acid and found to be dose dependent. Leaves extract had the highest total phenolic content[（206.17±1.95） mg GAE/g],followed by flowers,roots and stems extracts which were（117.08±3.10） mg GAE/g,（83.15±1.19） mg GAE/g,and （65.70±1.72） mg GAE/g,respectively.On the other hand,total flavonoids content also from leave had the highest value[（37.970±0.003） mg CEQ/g],followed by flowers,roots and stems extracts which were（35.200±0.002） mg CEQ/g,（24.350±0.006） mg CEQ/g,and（24.120±0.004） mg CEQ/ g,respectively.HPTLC bioautography analysis of phenolic and antioxidant substance revealed phenolic compounds.Phytochemical screening of E.hirta leaf extract revealed the presence of reducing sugars,terpenoids,alkaloids,steroids,tannins,flavanoids and phenolic compounds. Conclusions:These results suggeste that E.hirta have strong antioxidant potential.Further study is necessary for isolation and characterization of the active antioxidant agents,which can be used to treat various oxidative stress-related diseases.展开更多
Objective:To study the epidemiology of Helicobacter pylori(H.pylori) infection according to age group.Methods:H.pylori infection data among 1 965 consecutive patients referred to the Endoscopy Unit collected at Sungai...Objective:To study the epidemiology of Helicobacter pylori(H.pylori) infection according to age group.Methods:H.pylori infection data among 1 965 consecutive patients referred to the Endoscopy Unit collected at Sungai Petani Hospital for oesophagogastro-duodenoscopy(OGD). The patients were divided into 9 age groups(10-19,20-29,30-39,40-49,50-59,60-69,70-79, 80-89 and 90-99 years).In addition these groups were further divided into three minor group namely young adults(10-39),older adults(40-69) and geriatric groups(70-99).Results:Overall prevalence of infection of H.pylori was analyzed and found that the prevalence increase with age (P【0.05).When the patients divided by ethnic and gender group with age,prevalence rate among young adults and older adults significantly higher(P【0.05) compared to geriatric groups across all races and gender(P【0.05).Furthermore,significantly higher number of males were infected compared to female(P【0.05) but such trend was only observed among older adult groups.In addition,there is a significant differences in H.pylori infection prevalence rates among ethnic groups(highest in Indians adults,followed Chinese and low in Malays,P【0.05).Conclusions: The overall prevalence of H.pylori did increase with age group across ethnicity and gender,in Northern Peninsular Malaysia.展开更多
Objective:To elucidate its pharmacological activities and medicinal potential of extract of Etlingera elatior（E.elatior）.Methods:Phytochemical screening of the flower extract was done to determine the phytochemical ...Objective:To elucidate its pharmacological activities and medicinal potential of extract of Etlingera elatior（E.elatior）.Methods:Phytochemical screening of the flower extract was done to determine the phytochemical in the extract.The pharmacological study included the determination of antimicrobial activity and minimum inhibitory concentration（MIC） of metabolic flower extract.The antimicrobial activity of the extract was tested against medically important bacterial,yeast and fungal strains.Apart from that,the methanolic extract of E.elatior flower was further tested in vivo toxicity using the brine shrimp lethality test.Moreover,the flower extract was qualitatively screened for their free radical scavenging activity by 2,2-diphenyl-1- picrylhydrazyl radical（DPPH） assay.Results:The extract was effective on tested microorganisms and MIC values were in the range of 1.563-50.000 mg/mL.The brine shrimp lethality test exhibited no significant toxicity(LC<sub>50</sub>= 2.52 mg/mL) against Artemia salina.The E.elatior flower extract with high LC<sub>50</sub> value signified that this plant is not toxic to humans.While the phytochemical screening of the flower extract revealed the presence of the following compounds: flavonoids,terpenoids,saponin,tannins and carbohydrates whereas,alkaloids,anthraquinone and reducing sugars were absent.The concentration of the flower extract required for 50% inhibition of DPPH radical scavenging effect(IC<sub>50</sub>) were 9.14 mg/mL and 8.08 mg/mL for butylated hydroxytoluene 8.08 mg/mL.Conclusions:These findings indicate that the extract of E.elatior flower possesses pharmacological properties and potential to develop natural products based pharmaceuticals products.展开更多
Objective:To determine the major changes in the microstructure of Candida albicans(C. albicans) after treatment with Euphorbia hirta(E.hirta) L.leaf extract.Methods:Transmission electron microscopy was used to study t...Objective:To determine the major changes in the microstructure of Candida albicans(C. albicans) after treatment with Euphorbia hirta(E.hirta) L.leaf extract.Methods:Transmission electron microscopy was used to study the ultrastructural changes caused by E.hirta extract on C. albicans cells al various exposure time.Results:It was found that the main abnormalities were the alterations in morphology,lysis and complete collapse of the yeast cells after 36 h of exposure to the extract.Whereas the control cultures showed a typical morphology of Candida with a uniform central density,typically structured nucleus,and a cytoplasm with several elements of endomembrane system and enveloped by a regular,intact cell wall.Conclusions:The significant antifungal activity shown by this methanol extract of E.hirta L.suggests its potential against infections caused by C.albicans.The extract may be developed as an anticandidal agent.展开更多
Objective:To isolate Salmonella from curry samples and to evaluate the drug sensitivity of the food-borne Salmonella and its susceptibility to specific plant extracts.Methods:Salmonella was isolated from the curry sam...Objective:To isolate Salmonella from curry samples and to evaluate the drug sensitivity of the food-borne Salmonella and its susceptibility to specific plant extracts.Methods:Salmonella was isolated from the curry samples by standard microbiological methods and was confirmed by biochemical tests.The antibiotic susceptibility test was conducted by disc diffusion method using commercially available antibiotics such as ampicillin,tetracycline,chloramphenicol,kanamycin,and penicillin.In addition,the susceptibility of the food-borne Salmonella was also evaluated against the aqueous extracts of Camelia sinensis(L.) Theaceae(tea leaves) and the Trachyspermum ammi(L.) Apiaceae(ajwain or omum seeds).Results:Out of fifty curry samples,only seven samples were identified to have Salmonella contamination.The Salmonella isolates showed a significant drug resistance pattern except for kanamycin.The plant extracts showed a considerable antibacterial activity against the isolates,indicating the presence of antimicrobial principle which can be exploited after complete pharmacological investigations.Conclusions:The present study demonstrates the occurrence of Salmonella in the curry samples,and shows significant drug resistance against most of the commercially available antibiotics,except kanamycin.Antimicrobial effect of the plant extracts against the food-bone Salmonella suggests that dietary including medicinal herbs would be one strategy to manage food borne pathogens.展开更多
Objective:To investigate the toxicity of methanol extract of various parts(Root,Stem,Leaf, Flower and Fruit) of Lantana camara(L.Camara) in Artemia salina.Methods:The methanol extracts of L.camara were tested for in v...Objective:To investigate the toxicity of methanol extract of various parts(Root,Stem,Leaf, Flower and Fruit) of Lantana camara(L.Camara) in Artemia salina.Methods:The methanol extracts of L.camara were tested for in vivo brine shrimp lethality assay.Results:All the tested extract exhibited very low toxicity on brine shrimp larva.The results showed that the root extract was the most toxic part of L.camara and may have potential as anticancer agent.Conclusions: Methanolic extract of L.camara is relatively safe on short-term exposure.展开更多
Objective: To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis(M. tuberculosis) of a proteoliposome(PL)from Mycobacterium bovis Bacillus Calmette–Guerin...Objective: To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis(M. tuberculosis) of a proteoliposome(PL)from Mycobacterium bovis Bacillus Calmette–Guerin(BCG) with and without alum hydroxide(AL) as adjuvant(PLBCG-AL and PLBCG, respectively) in BALB/c mice.Methods: BALB/c mice were inoculated with phosphate buffer solution, BCG, PLBCG and PLBCG-AL. The humoral immunogenicity was determined by ELISA [immunoglobulin G(Ig G), Ig G1 and Ig G2a] and the cellular immunogenicity was evaluated in vivo by delayed type hypersensitivity. The humoral cross-reactive response against M. tuberculosis was determined by Western blot.Results: Sera from animals immunized with PLBCG-AL and PLBCG showed significant increase in specific total Ig G and Ig G1 antibodies and the presence of cross-reactive antibodies against M. tuberculosis antigens, which were more intense with the use of alum as adjuvant. Mice immunized with PLBCG and PLBCG-AL also showed a specific cellular response in vivo.Conclusions: The cellular and humoral immunogenicity of PLBCG and the capacity to induce cross-reactive responses against M. tuberculosis is in agreement with the protective capacity previously demonstrated by this vaccine candidate and supports the continuation of its evaluation in further stages.展开更多
AIM: To investigate the protein expression profi le of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations. METHODS: Immunohistochemical analysis of t...AIM: To investigate the protein expression profi le of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations. METHODS: Immunohistochemical analysis of tumor samples was performed to determine the protein expression profile of MMR protein. Germline mutation screening was carried out on peripheral blood samples. The entire exon regions of MLH1 and MSH2 geneswere amplifi ed by polymerase chain reaction, screened by denaturing high performance liquid chromatography (dHPLC) and analyzed by DNA sequencing to characterize the germline mutations. RESULTS: Three out of 34 tissue samples (8.8%) and four out of 34 tissue samples (11.8%) showed loss of nuclear staining by immunohistochemistry, indicating the absence of MLH1 and MSH2 protein expression in carcinoma cells, respectively. dHPLC analysis followed by DNA sequencing showed these samples to have germline mutations of MSH2 gene. However, no deleterious mutations were identifi ed in any of the 19 exons or coding regions of MLH1 gene, but we were able to identify MLH1 promoter polymorphism, -93G > A (rs1800734), in 21 out of 34 patients (61.8%). We identified one novel mutation, transversion mutation c.2005G > C, which resulted in a missense mutation (Gly669Arg), a transversion mutation in exon 1, c.142G > T, which resulted in a nonsense mutation (Glu48Stop) and splice-site mutation, c.2006-6T > C, which was adjacent to exon 13 of MSH2 gene. CONCLUSION: Germline mutations were identified in four Malaysian Lynch syndrome patients. Immunohistochemical analysis of tumor tissue proved to be a good pre-screening test before proceeding to germline mutation analysis of DNA MMR genes.展开更多
Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta(E.hirta)in MCF-7 cell line model using comet assay.Methods:The cytotoxicity of E.hirta extract was investigated by employing brine sh...Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta(E.hirta)in MCF-7 cell line model using comet assay.Methods:The cytotoxicity of E.hirta extract was investigated by employing brine shrimp lethality assay and the genotoxicity of E.hirta was assessed by using Comet assay.Results:Both toxicity tests exhibited significant toxicity result.In the comet assay,the E.hirta extract exhibited genotoxicity effects against MCF-7 DNA in a time-dependent manner by increasing mean percentage of DNA damage.The extract of E.hirta showed significant toxicity against brine shrimp with an LC_(50)value of 620.382μg/mL(24 h).Comparison with positive control potassium dichroniate signifies that cytotoxicity exhibited by the methanol extract might have moderate activity.Conclusion:The present work confirmed the cytotoxicity and genotoxicity of E.hirta.However,the observed toxicity of E.hta extracts needs to be confirmed in additional studies.展开更多
MircroRNAs(mi RNAs)are short non-coding RNAs with a length of approximately 20-22 nucleotides,which interact with their target mRNAs at 3’-untranslated region by partial pairing.The miRNAm-RNA interaction leads to in...MircroRNAs(mi RNAs)are short non-coding RNAs with a length of approximately 20-22 nucleotides,which interact with their target mRNAs at 3’-untranslated region by partial pairing.The miRNAm-RNA interaction leads to induction of mRNA degradation and eventually translational inhibition.Thus,mi RNAs play an important role in virtually all cellular processes,especially differentiation,proliferation,migration,and apoptosis.The deregulation of miRNAs may lead to serious diseases including cancer.There is mounting evidence demonstrating the participation of mi RNA regulation during carcinogenesis.In this review,we discuss an updated miRNA biogenesis,mechanisms involved in their deregulation,and their role in cancer development.This review also summarizes updated information on potential medicinal plants which regulate miRNA expression as a promising molecular miRNA therapeutic approach for cancers.展开更多
Objective:To investigate the cytotoxic effect of Elaeis guineensis methanol extract on MCF-7and Vero cell.Methods:In vitro cytotoxicity was evaluated in by MTT assay.Cell morphological changes were observed by using l...Objective:To investigate the cytotoxic effect of Elaeis guineensis methanol extract on MCF-7and Vero cell.Methods:In vitro cytotoxicity was evaluated in by MTT assay.Cell morphological changes were observed by using light microscope.Results:The MTT assay indicated that methanol extract of the plant exhibited significant cytotoxic effects on MCF-7.Morphological alteration of the cell lines after exposure with lilaeis guineensis extract were observed under phase contrast microscope in the dose dependent manner.Conclusions:The results suggest the probable use of the Elaeis guineensis methanol extract in preparing recipes for cancer-related ailments.Further studies on isolation of metabolites and their in vivo cytotoxicity are under investigation.展开更多
Objective:To compare the efficacy of three different tissue stains,namely haematoxylin and eosin(H&E),periodic-acid Schiff(PAS)and immunohistochemical(1HC)stains for detection of Entamoeba histolytica(E.histolytic...Objective:To compare the efficacy of three different tissue stains,namely haematoxylin and eosin(H&E),periodic-acid Schiff(PAS)and immunohistochemical(1HC)stains for detection of Entamoeba histolytica(E.histolytica)trophozoites in abscessed liver tissues of hamster.Methods:Amoebic liver abscess was experimentally induced in a hamster by injecting 1×10~6of axenically cultured virulent E.histolytica trophozoites(HM1-IMSS strain)into the portal vein.After a week post-inoculation,the hamster was sacrificed and the liver tissue sections were stained with H&E,PAS and IHC stains to delect the amoebic trophozoite.Results:The three stains revealed tissue necrosis and amoebic trophozoites,but with varying clarity.H&E and PAS stained the trophozoites pink and magenta,respectively,however it was difficult to differentiate the stained trophozoites from the macrophages because of their similarity in size and morphology.On the other hand,IHC stain revealed distinct brown appearance of the trophozoites in the infected liver tissues.Conclusions:It can be concluded that out of the three stains.IHC is the best for identification of E.histolytica trophozoites in tissue sections.展开更多
Objective: To investigate the status of Strongyloides(S.) stercoralis infections among migrant workers in Malaysia for the first time and identify risk factors.Methods: Four diagnostic methods were employed for the de...Objective: To investigate the status of Strongyloides(S.) stercoralis infections among migrant workers in Malaysia for the first time and identify risk factors.Methods: Four diagnostic methods were employed for the detection of S. stercoralis including microscopy, enzyme-linked immunosorbent assay(ELISA) using a commercial kit, ELISA using the rSs1a antigen and polymerase chain reaction(PCR). Low and semi-skilled workers from five working sectors(i.e. manufacturing, food service, agriculture and plantation, construction and domestic service) were tested on a voluntary basis. Results: The overall seroprevalence of S. stercoralis from 483 workers employing the ELISA commercial kit for IgG was 35.8%(n=173;95% CI: 31.5%-40.1%) whereas seroprevalence using the rSs1a-ELISA was 13.0%(n=63;95% CI: 10.0%-16.0%). Cross tabulation between the ELISA commercial kit and rSs1a-ELISA showed that only 6.4%(n=31;95% CI: 4.2%-8.6%) of the samples were positive in both tests. Microscopic examination of all 388 fecal samples were negative;however subsequent testing by a nested PCR against DNA from the same samples successfully amplified DNA from three male subjects(0.8%;3/388). Male workers, India and Myanmar nationality, food service occupation and those living in the hostel were statistically significant with seroprevalence(P<0.005). Conclusion: This is the first report on the epidemiology of S. stercoralis infections among the migrant workers in Malaysia. Our results highlight the importance of using appropriate diagnostic tools for detection. The presence of anti-S. stercoralis antibodies in the study population calls for improvements in personal hygiene and sanitation standards among migrant workers in Malaysia through control strategies including health education campaigns and programs aimed at increasing awareness and healthy behaviors.展开更多
Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remai...Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remaining class of effective antimalarial(artemisinin) in South East Asia may soon pose a significant threat. Hence, the identification of new antimalarial compounds with a novel mode of action is necessary to curb this problem. Protein kinase has been implicated as a valid target for drug development in diseases such as cancer and diabetes in humans. A similar approach is now recognized for the treatment of protozoan-related disease including malaria. Few Plasmodium protein kinases that are not only crucial for their survival but also have unique structural features have been identified as a potential target for drug development. In this review, studies on antimalarial drug development exploiting the size of Plasmodium protein kinase ATP gatekeeper over the past 15 years are mainly discussed. The ATP-binding site of Plasmodium protein kinases such as Pf CDPK1, Pf CDPK4, Pf PKG, Pf PK7, and Pf PI4K showed great potential for selective and multi-target inhibitions owing to their smaller or unique ATP-gatekeeper amino acid subunits compared to that of human protein kinase. Hence it is a feasible solution to identify a new class of active antimalarial agents with a novel mode of action and longer clinical life-span.展开更多
Objective:To determine the true prevalence of soil-transmitted helminth infections in the Malaysian aborigines using real-time PCR.Methods:A total of 122 aborigines from seven tribes were recruited from settlements an...Objective:To determine the true prevalence of soil-transmitted helminth infections in the Malaysian aborigines using real-time PCR.Methods:A total of 122 aborigines from seven tribes were recruited from settlements and nearby hospitals which served the communities,located in four states in Peninsular Malaysia.The stool samples were examined for the presence of soil-transmitted helminth using real-time PCR and microscopy.The latter included the direct wet mount and formalin-ether concentration technique(FECT).The infection load in FECT-positive samples was determined by the Kato-Katz method.Rotorgene real-time analyzer detected five helminth species using two sets of assays.Results:The real-time PCR detected soil-transmitted helminth in 98.4% samples(n=122),which were 1.56 times higher than by microscopy.Ascaris lumbricoides and Trichuris trichiura were detected in more than 90% of the samples,while hookworm was detected in 46.7%(Necator americanus) and 13.9%(Ancylostoma sp.)of the samples.Comparison with previous reports on the Malaysian aborigines showed that the real-time PCR markedly improved the detection of Ascaris lumbricoides,hookworm and Strongyloides stercoralis.The real-time PCR detected poly-helminths in 92.6%of the samples compared to 28.7% by microscopy.In addition,27 samples(22.1%) showed amplification of Strongyloides stercoralis DNA.Conclusions:The real-time PCR showed very high prevalence rates of soil-transmitted helminth infections in the aborigines and is the recommended method for epidemiological investigation of soiltransmitted helminth infections in this population.展开更多
Objective:To isolate and characterize RNA aptamers that are specific to human CD36 protein using systematic evolution of ligands by exponential enrichment(SELEX)technology to identify candidates for adjunct therapy to...Objective:To isolate and characterize RNA aptamers that are specific to human CD36 protein using systematic evolution of ligands by exponential enrichment(SELEX)technology to identify candidates for adjunct therapy to reverse the binding of Plasmodiuminfected erythrocytes.Methods:RNA aptamers were isolated using nitrocellulose membrane-based SELEX and binding analysis was screened using an electrophoretic mobility shift assay and enzyme-linked oligonucleotide assay.Results:Thirteen cycles of nitrocellulose membrane-based SELEX yielded three aptamers(RC60,RC25,RC04)exhibiting high binding against CD36 protein as shown on electrophoretic mobility shift assay.The sequence analysis revealed a G-quadruplex sequence within all the isolated aptamers that might contribute to aptamer binding and thermodynamic stability.The specificity assay further showed that RC60 and RC25 were highly specific to CD36.The competitive inhibition assay demonstrated that RC60 and RC25 shared a similar binding epitope recognized by m Ab FA6-152,a specific monoclonal antibody against CD36.Conclusions:RC60 and RC25 are promising candidates as anticytoadherence for severe malaria adjunct therapy.展开更多
BACKGROUND Pancreatic cancer is the most aggressive cancer type.Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients.AIM T...BACKGROUND Pancreatic cancer is the most aggressive cancer type.Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients.AIM To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation(ID:C5EOSEW5050ESA trademarked as Nuvastatic^(TM)),and gemcitabine combination on pancreatic xenograft model.METHODS Mice were randomly divided into six groups of 6 mice each(n=6)and given different treatments for 28 d.The study design consisted of a 2 x 3 factorial treatment structure,with gemcitabine(yes/no)by oral(at 1200 and 400 mg/kg per day).Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice.C5EOSEW5050ESA(200 or 400 mg/kg per day)was administered orally,while gemcitabine(10 mg/kg per 3 d)was given intraperitoneally either alone or in combination treatment.Histopathological analyses of vital organs,tumour tissues,and incidence of lethality were analysed.Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67,respectively.RESULTS No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group.C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment.Remarkably,a comparably greater response in a reduction in tumour growth,Ki-67 protein expression,and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents.CONCLUSION These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment.Thus,this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.展开更多
基金supported by the Ministry of Higher Education Malaysia for Fundamental Research Grant Scheme with Project Code:FRGS/1/2019/SKK11/USM/02/5。
文摘Burkholderia pseudomallei is a causative agent of melioidosis that can infect humans and animals in endemic countries,specifically in Southeast Asia and tropical Australia.A fundamental component for the pathogenesis of Burkholderia pseudomallei is the capability of the bacterium to enter,survive,replicate,and cause disease in a host cell by inducing the host cell fusion.Cell fusion results in multinucleated-giant cell formation,thus enabling the dissemination of Burkholderia pseudomallei intracellularly.cGAS reacts to Burkholderia pseudomallei infection by activating the cGAS-STING pathway and subsequently limiting host's aberrant cell division and cellular replication by inducing autophagic cell death.In this review,we discuss the host-pathogen interactions between the typeⅥsecretion system 5(T6SS-5)of Burkholderia pseudomallei and human cGAS pathway in melioidosis infections.Since T6SS-5 is a main virulent factor in Burkholderia pseudomallei and the c GAS pathway is vital for host immune response,elucidating their functions is important for better understanding the pathogenesis of Burkholderia pseudomallei.
基金Supported by the Ministry of Higher Education Malaysia for the Fundamental Research Grant Scheme,No. FRGS/1/2021/SKK06/USM/02/7
文摘BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.
文摘Objective:To evaluate the prevalence of multidrug resistant Staphylococcus aureus(S.aureus) in dairy products.Methods:Isolation and identification of S.aureus were performed in 3 dairybased food products.The isolates were tested for their susceptibility to 5 different common antimicrobial drugs.Results:Of 50 samples examined,5(10%) were contaminated with 5. aureus.Subsequently,the 5 isolates were subjected to antimicrobial resistance pattern using five antibiotic discs(methicillin,vancomycin,kanamycin,chloramphenicol and tetracycline).Sample 29 showed resistance to methicillin and vancomycin.Sample 18 showed intermediate response to tetracycline.The other samples were susceptible to all the antibiotics tested.Conclusions:The results provide preliminary data on sources of food contamination which may act as vehicles for the transmission of antimicrobial-resistant Staphylococcus.Therefore,it enables us to develop preventive strategies to avoid the emergence of new strains of resistant S.aureus.
基金Islamic Development Bank for the financial support with a master degree scholarship
文摘Objective:To assess antioxidant activities of different parts of Euphorbia hirta（E.hirta）,and to search for new sources of safe and inexpensive antioxidants.Methods:Samples of leaves,stems, flowers and roots from E.hirta were tested for total phenolic content,and flavonoids content and in vitro antioxidant activity by diphenyl-1-picrylhydrazyl（DPPH） assay and reducing power was measured using cyanoferrate method.Results:The leaves extract exhibited a maximum DPPH scavenging activity of（72.96±0.78）%followed by the flowers,roots and stems whose scavenging activities were（52.45±0.66）%,（48.59±0.97）%,and（44.42±0.94）%,respectively.The standard butylated hydroxytoluene（BHT） was（75.13±0.75）%.The IC<sub>50</sub>,for leaves,flowers,roots,stems and BHT were 0.803,0.972,0.989,1.358 and 0.794 mg/mL,respectively.The reducing power of the leaves extract was comparable with that of ascorbic acid and found to be dose dependent. Leaves extract had the highest total phenolic content[（206.17±1.95） mg GAE/g],followed by flowers,roots and stems extracts which were（117.08±3.10） mg GAE/g,（83.15±1.19） mg GAE/g,and （65.70±1.72） mg GAE/g,respectively.On the other hand,total flavonoids content also from leave had the highest value[（37.970±0.003） mg CEQ/g],followed by flowers,roots and stems extracts which were（35.200±0.002） mg CEQ/g,（24.350±0.006） mg CEQ/g,and（24.120±0.004） mg CEQ/ g,respectively.HPTLC bioautography analysis of phenolic and antioxidant substance revealed phenolic compounds.Phytochemical screening of E.hirta leaf extract revealed the presence of reducing sugars,terpenoids,alkaloids,steroids,tannins,flavanoids and phenolic compounds. Conclusions:These results suggeste that E.hirta have strong antioxidant potential.Further study is necessary for isolation and characterization of the active antioxidant agents,which can be used to treat various oxidative stress-related diseases.
基金S.Jo Thy Lachumy was supported by Universiti Sains Malaysia fellowship from Institute for Postgraduate Studies,Universiti Sains Malaysiasupported by USM Incentive Grant from University Sains Malaysia
文摘Objective:To study the epidemiology of Helicobacter pylori(H.pylori) infection according to age group.Methods:H.pylori infection data among 1 965 consecutive patients referred to the Endoscopy Unit collected at Sungai Petani Hospital for oesophagogastro-duodenoscopy(OGD). The patients were divided into 9 age groups(10-19,20-29,30-39,40-49,50-59,60-69,70-79, 80-89 and 90-99 years).In addition these groups were further divided into three minor group namely young adults(10-39),older adults(40-69) and geriatric groups(70-99).Results:Overall prevalence of infection of H.pylori was analyzed and found that the prevalence increase with age (P【0.05).When the patients divided by ethnic and gender group with age,prevalence rate among young adults and older adults significantly higher(P【0.05) compared to geriatric groups across all races and gender(P【0.05).Furthermore,significantly higher number of males were infected compared to female(P【0.05) but such trend was only observed among older adult groups.In addition,there is a significant differences in H.pylori infection prevalence rates among ethnic groups(highest in Indians adults,followed Chinese and low in Malays,P【0.05).Conclusions: The overall prevalence of H.pylori did increase with age group across ethnicity and gender,in Northern Peninsular Malaysia.
基金supported by Universiti Sains Malaysia fellowship from Institute for Postgraduate Studies,Universiti Sains Malaysia
文摘Objective:To elucidate its pharmacological activities and medicinal potential of extract of Etlingera elatior（E.elatior）.Methods:Phytochemical screening of the flower extract was done to determine the phytochemical in the extract.The pharmacological study included the determination of antimicrobial activity and minimum inhibitory concentration（MIC） of metabolic flower extract.The antimicrobial activity of the extract was tested against medically important bacterial,yeast and fungal strains.Apart from that,the methanolic extract of E.elatior flower was further tested in vivo toxicity using the brine shrimp lethality test.Moreover,the flower extract was qualitatively screened for their free radical scavenging activity by 2,2-diphenyl-1- picrylhydrazyl radical（DPPH） assay.Results:The extract was effective on tested microorganisms and MIC values were in the range of 1.563-50.000 mg/mL.The brine shrimp lethality test exhibited no significant toxicity(LC<sub>50</sub>= 2.52 mg/mL) against Artemia salina.The E.elatior flower extract with high LC<sub>50</sub> value signified that this plant is not toxic to humans.While the phytochemical screening of the flower extract revealed the presence of the following compounds: flavonoids,terpenoids,saponin,tannins and carbohydrates whereas,alkaloids,anthraquinone and reducing sugars were absent.The concentration of the flower extract required for 50% inhibition of DPPH radical scavenging effect(IC<sub>50</sub>) were 9.14 mg/mL and 8.08 mg/mL for butylated hydroxytoluene 8.08 mg/mL.Conclusions:These findings indicate that the extract of E.elatior flower possesses pharmacological properties and potential to develop natural products based pharmaceuticals products.
文摘Objective:To determine the major changes in the microstructure of Candida albicans(C. albicans) after treatment with Euphorbia hirta(E.hirta) L.leaf extract.Methods:Transmission electron microscopy was used to study the ultrastructural changes caused by E.hirta extract on C. albicans cells al various exposure time.Results:It was found that the main abnormalities were the alterations in morphology,lysis and complete collapse of the yeast cells after 36 h of exposure to the extract.Whereas the control cultures showed a typical morphology of Candida with a uniform central density,typically structured nucleus,and a cytoplasm with several elements of endomembrane system and enveloped by a regular,intact cell wall.Conclusions:The significant antifungal activity shown by this methanol extract of E.hirta L.suggests its potential against infections caused by C.albicans.The extract may be developed as an anticandidal agent.
基金Supported by Research Laboratory for Biotechnology,Department of Biotechnology,AIMST University,Malaysia
文摘Objective:To isolate Salmonella from curry samples and to evaluate the drug sensitivity of the food-borne Salmonella and its susceptibility to specific plant extracts.Methods:Salmonella was isolated from the curry samples by standard microbiological methods and was confirmed by biochemical tests.The antibiotic susceptibility test was conducted by disc diffusion method using commercially available antibiotics such as ampicillin,tetracycline,chloramphenicol,kanamycin,and penicillin.In addition,the susceptibility of the food-borne Salmonella was also evaluated against the aqueous extracts of Camelia sinensis(L.) Theaceae(tea leaves) and the Trachyspermum ammi(L.) Apiaceae(ajwain or omum seeds).Results:Out of fifty curry samples,only seven samples were identified to have Salmonella contamination.The Salmonella isolates showed a significant drug resistance pattern except for kanamycin.The plant extracts showed a considerable antibacterial activity against the isolates,indicating the presence of antimicrobial principle which can be exploited after complete pharmacological investigations.Conclusions:The present study demonstrates the occurrence of Salmonella in the curry samples,and shows significant drug resistance against most of the commercially available antibiotics,except kanamycin.Antimicrobial effect of the plant extracts against the food-bone Salmonella suggests that dietary including medicinal herbs would be one strategy to manage food borne pathogens.
基金Supported by a grant form Universiti Sains Malaysia University
文摘Objective:To investigate the toxicity of methanol extract of various parts(Root,Stem,Leaf, Flower and Fruit) of Lantana camara(L.Camara) in Artemia salina.Methods:The methanol extracts of L.camara were tested for in vivo brine shrimp lethality assay.Results:All the tested extract exhibited very low toxicity on brine shrimp larva.The results showed that the root extract was the most toxic part of L.camara and may have potential as anticancer agent.Conclusions: Methanolic extract of L.camara is relatively safe on short-term exposure.
基金Supported by the Long-Term Research Grant Scheme Grant,Department of Higher Education,Ministry of Education,Malaysia(Grant No.203.PPSK.67212002)as well as the Ministry of Science and Technology,Cuba
文摘Objective: To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis(M. tuberculosis) of a proteoliposome(PL)from Mycobacterium bovis Bacillus Calmette–Guerin(BCG) with and without alum hydroxide(AL) as adjuvant(PLBCG-AL and PLBCG, respectively) in BALB/c mice.Methods: BALB/c mice were inoculated with phosphate buffer solution, BCG, PLBCG and PLBCG-AL. The humoral immunogenicity was determined by ELISA [immunoglobulin G(Ig G), Ig G1 and Ig G2a] and the cellular immunogenicity was evaluated in vivo by delayed type hypersensitivity. The humoral cross-reactive response against M. tuberculosis was determined by Western blot.Results: Sera from animals immunized with PLBCG-AL and PLBCG showed significant increase in specific total Ig G and Ig G1 antibodies and the presence of cross-reactive antibodies against M. tuberculosis antigens, which were more intense with the use of alum as adjuvant. Mice immunized with PLBCG and PLBCG-AL also showed a specific cellular response in vivo.Conclusions: The cellular and humoral immunogenicity of PLBCG and the capacity to induce cross-reactive responses against M. tuberculosis is in agreement with the protective capacity previously demonstrated by this vaccine candidate and supports the continuation of its evaluation in further stages.
基金Supported by USM Research University Grant, No. 1001/CIPPT/813005
文摘AIM: To investigate the protein expression profi le of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations. METHODS: Immunohistochemical analysis of tumor samples was performed to determine the protein expression profile of MMR protein. Germline mutation screening was carried out on peripheral blood samples. The entire exon regions of MLH1 and MSH2 geneswere amplifi ed by polymerase chain reaction, screened by denaturing high performance liquid chromatography (dHPLC) and analyzed by DNA sequencing to characterize the germline mutations. RESULTS: Three out of 34 tissue samples (8.8%) and four out of 34 tissue samples (11.8%) showed loss of nuclear staining by immunohistochemistry, indicating the absence of MLH1 and MSH2 protein expression in carcinoma cells, respectively. dHPLC analysis followed by DNA sequencing showed these samples to have germline mutations of MSH2 gene. However, no deleterious mutations were identifi ed in any of the 19 exons or coding regions of MLH1 gene, but we were able to identify MLH1 promoter polymorphism, -93G > A (rs1800734), in 21 out of 34 patients (61.8%). We identified one novel mutation, transversion mutation c.2005G > C, which resulted in a missense mutation (Gly669Arg), a transversion mutation in exon 1, c.142G > T, which resulted in a nonsense mutation (Glu48Stop) and splice-site mutation, c.2006-6T > C, which was adjacent to exon 13 of MSH2 gene. CONCLUSION: Germline mutations were identified in four Malaysian Lynch syndrome patients. Immunohistochemical analysis of tumor tissue proved to be a good pre-screening test before proceeding to germline mutation analysis of DNA MMR genes.
基金supported by USM Short Term Grant(304/CIPPM/6312034)from Universiti Sains Malaysia
文摘Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta(E.hirta)in MCF-7 cell line model using comet assay.Methods:The cytotoxicity of E.hirta extract was investigated by employing brine shrimp lethality assay and the genotoxicity of E.hirta was assessed by using Comet assay.Results:Both toxicity tests exhibited significant toxicity result.In the comet assay,the E.hirta extract exhibited genotoxicity effects against MCF-7 DNA in a time-dependent manner by increasing mean percentage of DNA damage.The extract of E.hirta showed significant toxicity against brine shrimp with an LC_(50)value of 620.382μg/mL(24 h).Comparison with positive control potassium dichroniate signifies that cytotoxicity exhibited by the methanol extract might have moderate activity.Conclusion:The present work confirmed the cytotoxicity and genotoxicity of E.hirta.However,the observed toxicity of E.hta extracts needs to be confirmed in additional studies.
基金funded by Bridging Grant from Universiti Sains Malaysia,Pulau Pinang,Malaysia with grant number 304.CIPPM.6316068.
文摘MircroRNAs(mi RNAs)are short non-coding RNAs with a length of approximately 20-22 nucleotides,which interact with their target mRNAs at 3’-untranslated region by partial pairing.The miRNAm-RNA interaction leads to induction of mRNA degradation and eventually translational inhibition.Thus,mi RNAs play an important role in virtually all cellular processes,especially differentiation,proliferation,migration,and apoptosis.The deregulation of miRNAs may lead to serious diseases including cancer.There is mounting evidence demonstrating the participation of mi RNA regulation during carcinogenesis.In this review,we discuss an updated miRNA biogenesis,mechanisms involved in their deregulation,and their role in cancer development.This review also summarizes updated information on potential medicinal plants which regulate miRNA expression as a promising molecular miRNA therapeutic approach for cancers.
基金supported by USM Incentive Grant(GrantNumber:2009/167)from Universiti Sains Malaysia
文摘Objective:To investigate the cytotoxic effect of Elaeis guineensis methanol extract on MCF-7and Vero cell.Methods:In vitro cytotoxicity was evaluated in by MTT assay.Cell morphological changes were observed by using light microscope.Results:The MTT assay indicated that methanol extract of the plant exhibited significant cytotoxic effects on MCF-7.Morphological alteration of the cell lines after exposure with lilaeis guineensis extract were observed under phase contrast microscope in the dose dependent manner.Conclusions:The results suggest the probable use of the Elaeis guineensis methanol extract in preparing recipes for cancer-related ailments.Further studies on isolation of metabolites and their in vivo cytotoxicity are under investigation.
基金Supported by a grant from Universiti Sains Malaysia(grant No.1001/PPSK/813009)received financial support through the USM Fellowship
文摘Objective:To compare the efficacy of three different tissue stains,namely haematoxylin and eosin(H&E),periodic-acid Schiff(PAS)and immunohistochemical(1HC)stains for detection of Entamoeba histolytica(E.histolytica)trophozoites in abscessed liver tissues of hamster.Methods:Amoebic liver abscess was experimentally induced in a hamster by injecting 1×10~6of axenically cultured virulent E.histolytica trophozoites(HM1-IMSS strain)into the portal vein.After a week post-inoculation,the hamster was sacrificed and the liver tissue sections were stained with H&E,PAS and IHC stains to delect the amoebic trophozoite.Results:The three stains revealed tissue necrosis and amoebic trophozoites,but with varying clarity.H&E and PAS stained the trophozoites pink and magenta,respectively,however it was difficult to differentiate the stained trophozoites from the macrophages because of their similarity in size and morphology.On the other hand,IHC stain revealed distinct brown appearance of the trophozoites in the infected liver tissues.Conclusions:It can be concluded that out of the three stains.IHC is the best for identification of E.histolytica trophozoites in tissue sections.
基金funded by University of Malaya,PPP grant(PG040-2014A)Fundamental Research Grant Scheme(FRGS)from Ministry of Higher Education(FP015-2014B)+1 种基金UM/MoHE High Impact Research Grant(UM.C/625/1/HIR/MOHE/MED/23)Universiti Sains Malaysia,Malaysian Ministry of Higher Education grant(HICoE 311/CIPPM/4401005)
文摘Objective: To investigate the status of Strongyloides(S.) stercoralis infections among migrant workers in Malaysia for the first time and identify risk factors.Methods: Four diagnostic methods were employed for the detection of S. stercoralis including microscopy, enzyme-linked immunosorbent assay(ELISA) using a commercial kit, ELISA using the rSs1a antigen and polymerase chain reaction(PCR). Low and semi-skilled workers from five working sectors(i.e. manufacturing, food service, agriculture and plantation, construction and domestic service) were tested on a voluntary basis. Results: The overall seroprevalence of S. stercoralis from 483 workers employing the ELISA commercial kit for IgG was 35.8%(n=173;95% CI: 31.5%-40.1%) whereas seroprevalence using the rSs1a-ELISA was 13.0%(n=63;95% CI: 10.0%-16.0%). Cross tabulation between the ELISA commercial kit and rSs1a-ELISA showed that only 6.4%(n=31;95% CI: 4.2%-8.6%) of the samples were positive in both tests. Microscopic examination of all 388 fecal samples were negative;however subsequent testing by a nested PCR against DNA from the same samples successfully amplified DNA from three male subjects(0.8%;3/388). Male workers, India and Myanmar nationality, food service occupation and those living in the hostel were statistically significant with seroprevalence(P<0.005). Conclusion: This is the first report on the epidemiology of S. stercoralis infections among the migrant workers in Malaysia. Our results highlight the importance of using appropriate diagnostic tools for detection. The presence of anti-S. stercoralis antibodies in the study population calls for improvements in personal hygiene and sanitation standards among migrant workers in Malaysia through control strategies including health education campaigns and programs aimed at increasing awareness and healthy behaviors.
文摘Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remaining class of effective antimalarial(artemisinin) in South East Asia may soon pose a significant threat. Hence, the identification of new antimalarial compounds with a novel mode of action is necessary to curb this problem. Protein kinase has been implicated as a valid target for drug development in diseases such as cancer and diabetes in humans. A similar approach is now recognized for the treatment of protozoan-related disease including malaria. Few Plasmodium protein kinases that are not only crucial for their survival but also have unique structural features have been identified as a potential target for drug development. In this review, studies on antimalarial drug development exploiting the size of Plasmodium protein kinase ATP gatekeeper over the past 15 years are mainly discussed. The ATP-binding site of Plasmodium protein kinases such as Pf CDPK1, Pf CDPK4, Pf PKG, Pf PK7, and Pf PI4K showed great potential for selective and multi-target inhibitions owing to their smaller or unique ATP-gatekeeper amino acid subunits compared to that of human protein kinase. Hence it is a feasible solution to identify a new class of active antimalarial agents with a novel mode of action and longer clinical life-span.
基金provided by the Malaysian Ministry of Education under the Higher Institution Centre of Excellence Program(INFORMM HICo E No.311/CIPPM/4401005)LongTeam Research Grant Schemes(Ref.No.203/PSK/6722002 and 203/PPSK/67212002)
文摘Objective:To determine the true prevalence of soil-transmitted helminth infections in the Malaysian aborigines using real-time PCR.Methods:A total of 122 aborigines from seven tribes were recruited from settlements and nearby hospitals which served the communities,located in four states in Peninsular Malaysia.The stool samples were examined for the presence of soil-transmitted helminth using real-time PCR and microscopy.The latter included the direct wet mount and formalin-ether concentration technique(FECT).The infection load in FECT-positive samples was determined by the Kato-Katz method.Rotorgene real-time analyzer detected five helminth species using two sets of assays.Results:The real-time PCR detected soil-transmitted helminth in 98.4% samples(n=122),which were 1.56 times higher than by microscopy.Ascaris lumbricoides and Trichuris trichiura were detected in more than 90% of the samples,while hookworm was detected in 46.7%(Necator americanus) and 13.9%(Ancylostoma sp.)of the samples.Comparison with previous reports on the Malaysian aborigines showed that the real-time PCR markedly improved the detection of Ascaris lumbricoides,hookworm and Strongyloides stercoralis.The real-time PCR detected poly-helminths in 92.6%of the samples compared to 28.7% by microscopy.In addition,27 samples(22.1%) showed amplification of Strongyloides stercoralis DNA.Conclusions:The real-time PCR showed very high prevalence rates of soil-transmitted helminth infections in the aborigines and is the recommended method for epidemiological investigation of soiltransmitted helminth infections in this population.
基金supported by an Exploratory Research Grant Scheme(ERGS203/CIPPM/6730106)+2 种基金Higher Institution Centre of Excellent(HICo E311/CIPPM/4401005)from the Malaysian,Ministry of Higher EducationUniversiti Sains Malaysia Fellowship Scheme.
文摘Objective:To isolate and characterize RNA aptamers that are specific to human CD36 protein using systematic evolution of ligands by exponential enrichment(SELEX)technology to identify candidates for adjunct therapy to reverse the binding of Plasmodiuminfected erythrocytes.Methods:RNA aptamers were isolated using nitrocellulose membrane-based SELEX and binding analysis was screened using an electrophoretic mobility shift assay and enzyme-linked oligonucleotide assay.Results:Thirteen cycles of nitrocellulose membrane-based SELEX yielded three aptamers(RC60,RC25,RC04)exhibiting high binding against CD36 protein as shown on electrophoretic mobility shift assay.The sequence analysis revealed a G-quadruplex sequence within all the isolated aptamers that might contribute to aptamer binding and thermodynamic stability.The specificity assay further showed that RC60 and RC25 were highly specific to CD36.The competitive inhibition assay demonstrated that RC60 and RC25 shared a similar binding epitope recognized by m Ab FA6-152,a specific monoclonal antibody against CD36.Conclusions:RC60 and RC25 are promising candidates as anticytoadherence for severe malaria adjunct therapy.
基金Supported by the NKEA Research Grant Scheme (NRGS) by the Ministry of Agriculture MalaysiaNo. 304/CIPPM/650736/k123
文摘BACKGROUND Pancreatic cancer is the most aggressive cancer type.Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients.AIM To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation(ID:C5EOSEW5050ESA trademarked as Nuvastatic^(TM)),and gemcitabine combination on pancreatic xenograft model.METHODS Mice were randomly divided into six groups of 6 mice each(n=6)and given different treatments for 28 d.The study design consisted of a 2 x 3 factorial treatment structure,with gemcitabine(yes/no)by oral(at 1200 and 400 mg/kg per day).Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice.C5EOSEW5050ESA(200 or 400 mg/kg per day)was administered orally,while gemcitabine(10 mg/kg per 3 d)was given intraperitoneally either alone or in combination treatment.Histopathological analyses of vital organs,tumour tissues,and incidence of lethality were analysed.Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67,respectively.RESULTS No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group.C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment.Remarkably,a comparably greater response in a reduction in tumour growth,Ki-67 protein expression,and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents.CONCLUSION These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment.Thus,this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.
