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Fulltext Tumour-Associated Macrophages (TAMs) in Colon Cancer and How to Reeducate Them

Yahaya MAF, Lila MAM, Ismail S, Zainol M, Afizan NARNM

J Immunol Res, 2019;2019:2368249.
PMID: 30931335 DOI: 10.1155/2019/2368249

Tumour-associated macrophage (TAM) serves as the site in which most inflammatory cells coreside. It plays an important role in determining the progression and metastasis of a tumour. The characteristic of TAM is largely dependent on the stimuli present in its tumour microenvironment (TME). Under this environment, however, M2 macrophages are found to be in abundance compared to M1 macrophages which later promote tumour progression. Numerous studies have elucidated the relationship between TAM and the progression of tumour; hence, TAM has now been the subject of interest among researchers for anticancer therapy. This review discusses the role of TAM in colorectal cancer (CRC) and some of the potential candidates that could reeducate TAM to fight against CRC. It is with hope that this review will serve as the foundation in understanding TAM in CRC and helping other researchers to select the most suitable candidate to reeducate TAM that could assist in enhancing the tumouricidal activity of M1 macrophage and eventually repress the development of CRC.
Fulltext Association between Mannheimia haemolytica infection with reproductive physiology and performance in small ruminants: A review

Jesse FFA, Amira NA, Isa KM, Maqbool A, Ali NM, Chung ELT, et al.

Vet World, 2019 Jul;12(7):978-983.
PMID: 31528021 DOI: 10.14202/vetworld.2019.978-983

Mannheimiosis or pneumonic pasteurellosis commonly occurs in small ruminants. Mannheimiosis is caused by Mannheimia haemolytica (M. haemolytica) a Gram-negative coccobacillus producing acute febrile and infectious condition resulting in death of animal if not diagnosed and treated promptly. M. haemolytica serotype A2 is a commensal of the nasopharynx, gaining access to the lungs when host defenses are compromised by stress or infection in small ruminants. Till date, there is a vast literature and research that has been conducted on the pathogenesis of M. haemolytica invariably on respiratory system and its related immune system and mechanisms. From the clinical point of view, infection or diseases involving vital organs will systemically affect the production and performance of the infected animal. Therefore, there is a huge gap of knowledge and research to answer the question whether there is any association between M. haemolytica infection with reproductive physiology and performance in small ruminants and how it affects the productivity level. This review will explore the possibilities of involvement and new potential research to be carried out to determine the involvement of male and female reproductive system with M. haemolytica infection among small ruminants.
Responses of testosterone hormone and important inflammatory cytokines in bucks after challenge with Mannheimia haemolytica A2 and its LPS endotoxin

Azhar NA, Paul BT, Jesse FFA, Chung ELT, Isa KM, Lila MAM, et al.

Trop Anim Health Prod, 2021 Apr 03;53(2):242.
PMID: 33811523 DOI: 10.1007/s11250-021-02683-6

Previous studies have shown that Mannheimia haemolytica A2 is the principal microorganism causing pneumonic mannheimiosis, a major bacterial respiratory disease among sheep and goats. The effect of this bacteria on the respiratory system is well-established. However, its effect on the reproductive physiology remains unclear. Therefore, this study aimed to determine the alterations in the level of pro-inflammatory cytokines and testosterone hormone post-inoculation with M. haemolytica serotype A2 and its lipopolysaccharide (LPS) endotoxin which were hypothesized to affect the reproductive functions of bucks. Twelve clinically healthy adult male goats were divided equally into three groups. Goats in group 1 were treated with 2 ml of sterile phosphate-buffered saline (PBS) pH 7.0 intranasally (negative control), group 2 with 2 ml of 109 colony-forming unit (CFU) of M. haemolytica serotype A2 intranasally (positive control), and group 3 were treated with 2 ml of lipopolysaccharide extracted from 109 CFU of M. haemolytica serotype A2 intravenously. Following inoculation, blood samples were collected via jugular venipuncture into plain tubes at pre-determined intervals for serum collection to determine the concentration of interleukin (IL)-1β, IL6, tumor necrosis factor (TNF)-α, and testosterone hormone by using commercial ELISA test kits. Results from this study demonstrated that the inoculation of M. haemolytica A2 and its LPS increases the concentration of pro-inflammatory cytokines but decreases the concentration of testosterone hormone in challenged animals at most time points throughout the 56 days experimental period (p < 0.05). This study suggests that the M. haemolytica A2 and its LPS could alter the concentration of pro-inflammatory cytokines and testosterone hormone, which in turn, may negatively affect the reproductive functions of bucks.
Fulltext Seroprevalence of small ruminant caprine arthritis encephalitis lentivirus among goats from selected small ruminant farms in Selangor, Malaysia

Jesse FFA, Bitrus AA, Abba Y, Raju VN, Hambali IU, Peter ID, et al.

Vet World, 2018 Feb;11(2):172-176.
PMID: 29657399 DOI: 10.14202/vetworld.2018.172-176

Background and Aim: Caprine arthritis encephalitis (CAE) is an important viral disease of small ruminants particularly in dairy goats with severe social and economic implication. Hence, this study was designed to determine the seroprevalence of CAE virus (CAEV) among goat population in selected small ruminant farms in Selangor and the risk factors associated with the occurrence of the disease.
Materials and Methods: Blood samples were collected from a total of 91 goats selected at random. Blood serum was harvested and used for competitive enzyme-linked immunosorbent assay test to detect antibodies against CAE virus.
Results: The result obtained showed that 8/91 (8.8%) of the goats were seropositive for CAEV. In addition, biosecurity management, source of origin and sex of the animal were observed to be important risk factors associated with the occurrence of CAE in goats.
Conclusion: The findings of this study affirmed that the seroprevalence of CAEV infection among goat population in small ruminant farms in Selangor, Malaysia, is low. However, there is need to institute strict control measures such as testing and culling positive animals or separation of infected animals from those that tested negative to the disease for effective eradication of the disease.
Fulltext Hemogram responses in goats toward challenged with Corynebacterium pseudotuberculosis and its immunogen mycolic acids

Odhah MN, Abdullah FFJ, Haron AW, Lila MAM, Zamri-Saad M, Khuder Z, et al.

Vet World, 2017 Jun;10(6):655-661.
PMID: 28717318 DOI: 10.14202/vetworld.2017.655-661

AIM: This study was conducted to analyze the changes in blood profile of goats inoculated with Corynebacterium pseudotuberculosis and its immunogen mycolic acid (MA) extract.
MATERIALS AND METHODS: A total of 12 clinically healthy crossbred Boer female goats were divided into three groups; A, B and C (4 goats each per group). Group A was inoculated with 2 ml sterile phosphate buffered saline via intradermal route as the negative control group whilst Group B was inoculated with 2 ml of MA extract (1 g/ml) intradermally and Group C was then inoculated with 2 ml (1×10(9)) colony forming unit of active C. pseudotuberculosis intradermally. Blood sample was collected aseptically from the jugular vein periodically for complete blood count (CBC) analysis throughout the experimental period (3 months).
RESULT: A significant decrease (p<0.05) was observed in red blood cells, hemoglobin (Hb), packed cell volume, mean corpuscular volume and mean corpuscular Hb concentration in Groups B and C as compared to the control while WBCs, neutrophil, lymphocyte and basophil showed a significant increase (p<0.05) as compared to the control.
CONCLUSION: The inoculation of C. pseudotuberculosis and MA resulted in a significant change in the CBC, thereby, indicating that MA has a role in caseous lymphadenitis pathogenesis.
Fulltext Antitumor and antioxidant effects of Clinacanthus nutans Lindau in 4 T1 tumor-bearing mice

Nik Abd Rahman NMA, Nurliyana MY, Afiqah MNFNN, Osman MA, Hamid M, Lila MAM

BMC Complement Altern Med, 2019 Nov 29;19(1):340.
PMID: 31783838 DOI: 10.1186/s12906-019-2757-4

BACKGROUND: Clinacanthus nutans Lindau (C. nutans) is a species of in Acanthaceae family and primarily used in South East Asian countries. C. nutans is well known as Sabah snake grass in Malaysia, and its leaves have diverse medicinal potential in conventional applications, including cancer treatments. On the basis of literature search, there is less conclusive evidence of the involvement of phytochemical constituents in breast cancer, in particular, animal tumor models. The current study aimed to determine the antitumor and antioxidant activities of C. nutans extract in 4 T1 tumor-bearing mice.
METHODS: C. nutans leaves were subjected to methanol extraction and divided into two different concentrations, 200 mg/kg (low-dose) and 1000 mg/kg (high-dose). The antitumor effects of C. nutans extracts were assessed using bone marrow smearing, clonogenic, and splenocyte immunotype analyses. In addition, hematoxylin and eosin, tumor weight and tumor volume profiles also used to indicate apoptosis appearance. Serum cytokine levels were examined using ELISA assay. In addition, nitric oxide assay reflecting antioxidant activity was performed.
RESULTS: From the results obtained, the methanol extract of C. nutans leaves at 200 mg/kg (P
Fulltext Epidemiology and clinico-pathological characteristics of current goat pox outbreak in North Vietnam

Pham TH, Lila MAM, Rahaman NYA, Lai HLT, Nguyen LT, Do KV, et al.

BMC Vet Res, 2020 May 06;16(1):128.
PMID: 32375821 DOI: 10.1186/s12917-020-02345-z

BACKGROUND: In view of the current swine fever outbreak and the government aspiration to increase the goat population, a need arises to control and prevent outbreaks of goat pox. Despite North Vietnam facing sporadic cases of goat pox, this most recent outbreak had the highest recorded morbidity, mortality and case fatality rate. Thus, owing to the likelihood of a widespread recurrence of goat pox infection, an analysis of that outbreak was done based on selected signalment, management and disease pattern (signs and pathology) parameters. This includes examination of animals, inspection of facilities, tissue sampling and analysis for confirmation of goatpox along with questionaires.
RESULTS: It was found that the susceptible age group were between 3 and 6 months old kids while higher infection rate occurred in those under the free-range rearing system. The clinical signs of pyrexia, anorexia, nasal discharge and lesions of pocks were not restricted to the skin but have extended into the lung and intestine. The pathogen had been confirmed in positive cases via PCR as goat pox with prevalence of 79.69%.
CONCLUSIONS: The epidemiology of the current goat pox outbreak in North Vietnam denotes a significant prevalence which may affect the industry. This signals the importance of identifying the salient clinical signs and post mortem lesions of goat pox at the field level in order to achieve an effective control of the disease.
Fulltext An association of Orf virus infection among sheep and goats with herd health programme in Terengganu state, eastern region of the peninsular Malaysia

Bala JA, Balakrishnan KN, Abdullah AA, Adamu L, Noorzahari MSB, May LK, et al.

BMC Vet Res, 2019 Jul 18;15(1):250.
PMID: 31319873 DOI: 10.1186/s12917-019-1999-1

BACKGROUND: Orf virus causes a scabby skin lesions which decreases productivity in small ruminants. The unknown status of this disease in the eastern region of Peninsular Malaysia warrants a study to determine sero-prevalence of orf with regards to farmers' compliance level towards the Herd Health Program (HHP) programme.
RESULTS: Out of 504 animals, 115 were positive for Orf-virus antibodies. An overall prevalence rate of 22.8% indicated a high prevalence of orf disease in this region. It was observed that 25.1% (92/367) of goats were positive and 16.8% (23/137) of sheep sero-converted for Orf virus antibody. Several factors were measured for their possible association with prevalence of Orf virus infection. The prevalence was higher in LY farm, JC breed, kid and female animals, and in the presence of disease lesion. Chi-square analysis showed a significant association of three risk factors which are species, age and sex of the animals (P 0.05). Farms surveyed usually practised intensive management system, keeping animals in the shade at all time, due to limited availability of suitable land as a free-range grazing area. An interview with small holder farmers revealed a lack of awareness of the main goals of herd health programme. An overall compliance level of 42.7% was observed for all HHP parameters. Among the 14 main components of HHP modules, animal identification had recorded highest compliance level (84.62%) while milking management recorded the least compliance (- 82.69%). That explained why there was a high sporadic prevalence of Orf infection in this region.
CONCLUSION: Good herd health supervision is a rehearsal target to prevent an outbreak and the spread of diseases thus reduces economic losses among farmers. Therefore, a good herd health programme should be in place, in order to prevent and control disease transmission as well as to improve herd immunity.
Fulltext Molecular phylogenetics of a recently isolated goat pox virus from Vietnam

Pham TH, Rahaman NYA, Lila MAM, Lai HLT, Nguyen LT, Van Nguyen G, et al.

BMC Vet Res, 2021 Mar 08;17(1):115.
PMID: 33685458 DOI: 10.1186/s12917-021-02777-1

BACKGROUND: After a decade of silence, an outbreak of the contagious and Asian endemic disease, goat pox re-emerged in North Vietnam affecting more than 1800 heads with a mortality rate of 6.5%. The inevitable impact of goat pox on hide quality, breeding, chevon and milk production has resulted in a significant economic losses to the developing goat industry of Vietnam. In the act of establishing an effective control of this devastating disease, tracing the source of re-emergence via a phylogenetic study was carried out to reveal their genetic relatedness. Either skin scab or papule from the six affected provinces were collected, cultured into Vero cells followed by restricted enzyme digestion of targeted P32 gene DNA encoding. The P32 gene was then cloned and transformed into E.coli competent cells for further sequencing.
RESULTS: The isolated sequence is deposited into GenBank under Accession No. MN317561/VNUAGTP1. The phylogenetic tree revealed high similarity of nucleotide and amino acid sequences to references goat pox strains accounting for 99.6 and 99.3, respectively. The Vietnamese strain is clustered together with currently circulating goat pox virus in China, India and Pakistan which suggested the origin of South China.
CONCLUSIONS: This Vietnam isolate is clustered together with other Asian goat pox strains indicating the dissemination of a common goat pox virus within this continent.
Clinico-pathology and hemato-biochemistry responses in buffaloes infected with Pasteurella multocida type B:2 immunogen outer membrane protein

Chung ELT, Abdullah FFJ, Marza AD, Saleh WMM, Ibrahim HH, Abba Y, et al.

Microb Pathog, 2017 Jan;102:89-101.
PMID: 27894962 DOI: 10.1016/j.micpath.2016.11.015

The aim of this study was to investigate the clinico-pathology and haemato-biochemistry alterations in buffaloes inoculated with Pasteurella multocida type B:2 immunogen outer membrane protein via subcutaneous and oral routes. Nine buffalo heifers were divided equally into 3 treatment groups. Group 1 was inoculated orally with 10 mL of phosphate buffer saline (PBS); Group 2 and 3 were inoculated with 10 mL of outer membrane protein broth subcutaneously and orally respectively. Group 2 buffaloes showed typical haemorrhagic septicaemia clinical signs and were only able to survive for 72 h of the experiment. However, Group 3 buffaloes were able to survive throughout the stipulated time of 21 days of experiment. There were significant differences (p 0.05) in edema between groups except for the lung. This study was a proof that oral route infection of Pasteurella multocida type B:2 immunogen outer membrane protein can be used to stimulate host cell.
Establishment of lung auscultation scoring method and responses of acute phase proteins and heat shock proteins in vaccinated and non-vaccinated goats

Jesse FFA, Chung ELT, Abba Y, Muniandy KV, Tan AHAR, Maslamany D, et al.

Trop Anim Health Prod, 2019 Feb;51(2):289-295.
PMID: 30088124 DOI: 10.1007/s11250-018-1683-7

Pneumonic pasteurellosis is an economically important infectious disease in the small ruminant industry which causes sudden death and loss for farmers. Nonetheless, this disease is still a common sight in sheep and goats in Malaysia, probably due to the unpopular usage of pasteurellosis vaccine or inappropriate vaccination practices. The aim of this study was designed to classify the severity of pneumonia via the establishment of auscultation scoring method and to quantify the acute phase proteins and heat shock proteins responses from vaccinated and non-vaccinated goats. Goat farms, consist of vaccinated and non-vaccinated farms, were selected in this study: where 15 clinically normal healthy goats and 9 pneumonic goats were selected from vaccinated farms whereas 15 clinically normal healthy goats and 31 pneumonic goats from non-vaccinated farms were selected for this study. Crackle lung sounds were not detected in both vaccinated and non-vaccinated normal goats. However, vaccinated pneumonic goats showed mild crackle lung sound while non-vaccinated pneumonic goats exhibited moderate crackle lung sound. There were significant increases (p
Responses of pro-inflammatory cytokines, acute phase proteins and cytological analysis in serum and cerebrospinal fluid during haemorrhagic septicaemia infection in buffaloes

Chung ELT, Jesse FFA, Marza AD, Ibrahim HH, Abba Y, Zamri-Saad M, et al.

Trop Anim Health Prod, 2019 Jul;51(6):1773-1782.
PMID: 30919320 DOI: 10.1007/s11250-019-01870-w

Sudden death is usually the main finding in field animals during haemorrhagic septicaemia outbreaks caused by Pasteurella multocida type B:2 that causes acute, fatal and septicaemic disease in cattle and buffaloes. This situation may be due to failure in early detection of the disease where early treatment of antibiotics may improve the prognosis of the animal and other surviving animals. Thus, there is a grey area on the knowledge on the potential usage of pro-inflammatory cytokines and acute phase proteins as early biomarkers in the diagnosis of haemorrhagic septicaemia. In addition, exploration of the cerebrospinal fluid during infection has never been studied before. Therefore, this study was designed to fill up the grey areas in haemorrhagic septicaemia research. Twenty-one buffalo calves were divided into seven treatment groups where group 1 was inoculated orally with 10 mL of sterile phosphate-buffered saline pH 7 which act as a negative control group. Groups 2 and 3 were inoculated orally and subcutaneously with 10 mL of 1012 colony-forming unit of P. multocida type B:2. Group 4 and 5 buffaloes were inoculated orally and intravenously with 10 mL of lipopolysaccharide broth. Groups 6 and 7 were administered orally and subcutaneously with 10 mL of outer membrane protein broth. During the post-infection period of 21 days, blood and cerebrospinal fluid were sampled for the analyses of pro-inflammatory cytokines, acute phase proteins and cytological examination. Buffalo calves infected with P. multocida and its immunogens via different routes of inoculation showed significant changes (p
Corrigendum to "The ability of lipopolysaccharide (LPS) of Pasteurella multocida B:2 to induce clinical and pathological lesions in the nervous system of buffalo calves following experimental inoculation"[Microb. Pathog. 104 (2017) 340-347]

Marza AD, Abdullah FFJ, Ahmed IM, Chung ELT, Ibrahim HH, Zamri-Saad M, et al.

Microb Pathog, 2018 01;114:494.
PMID: 29074087 DOI: 10.1016/j.micpath.2017.10.011
Fulltext Further Insights Into Caprine Arthritis Encephalitis (CAE): The Current Status of Seroprevalence Among Small Ruminants in Two Selected States of Peninsular Malaysia

Paul BT, Hashi HA, Burhannuddin NN, Chung ELT, Jesse FFA, Lila MAM, et al.

Trop Life Sci Res, 2021 Jun;32(2):83-96.
PMID: 34367516 DOI: 10.21315/tlsr2021.32.2.6

Caprine arthritis-encephalitis virus (CAEV) is a member of the genus lentivirus causing caprine arthritis-encephalitis (CAE), a chronic inflammatory condition affecting the lungs, joints, udder and central nervous system of small ruminants such as sheep and goats. CAE is distributed worldwide and is recognised as a significant cause of morbidity and decreased milk production in dairy goats. Earlier studies highlighted the clinicopathological features and supplied preliminary serological evidence for the existence of CAE among selected goat herds in Malaysia. Therefore, this study aims to provide further insights into the seroprevalence and contributing factors of CAE among sheep and goat herds in two states of Peninsular Malaysia. The blood samples and biodata were randomly collected from a total of 262 individual sheep (40) and goat (222) in seven smallholder farms. Blood sera were tested for specific anti-CAEV antibodies using Qayee-Bio CAEV sandwich-ELISA test kits according to standard procedures. Our results of the study revealed 21.4% (95% CI: 15.8-28.6) apparent and 20.6% (95% CI: 14.5-27.8) true seroprevalence with significant differences (p < 0.05) in seroconversion rates between the states, farms, production systems and breeds of small ruminants. The prevalence of CAE in the Malaysian Peninsular is a potential threat to the small ruminant industry and developing agricultural economy. Further studies are required to determine the genetic characteristics, distribution and risk factors of CAEV for effective prevention and control in Malaysia.

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