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Dioxin risk assessment: mechanisms of action and possible toxicity in human health

Tavakoly Sany SB, Hashim R, Salleh A, Rezayi M, Karlen DJ, Razavizadeh BB, et al.

Environ Sci Pollut Res Int, 2015 Dec;22(24):19434-50.
PMID: 26514567 DOI: 10.1007/s11356-015-5597-x

Dioxin-like compounds (DLCs) have been classified by the World Health Organization (WHO) as one of the most persistent toxic chemical substances in the environment, and they are associated with several occupational activities and industrial accidents around the world. Since the end of the 1970s, these toxic chemicals have been banned because of their human toxicity potential, long half-life, wide dispersion, and they bioaccumulate in the food web. This review serves as a primer for environmental health professionals to provide guidance on short-term risk assessment of dioxin and to identify key findings for health and exposure assessment based on policies of different agencies. It also presents possible health effects of dioxins, mechanisms of action, toxic equivalency factors (TEFs), and dose-response characterization. Key studies related to toxicity values of dioxin-like compounds and their possible human health risk were identified through PubMed and supplemented with relevant studies characterized by reviewing the reference lists in the review articles and primary literature. Existing data decreases the scope of analyses and models in relevant studies to a manageable size by focusing on the set of important studies related to the perspective of developing toxicity values of DLCs.
Fulltext Antioxidant Biomaterials in Cutaneous Wound Healing and Tissue Regeneration: A Critical Review

Fadilah NIM, Phang SJ, Kamaruzaman N, Salleh A, Zawani M, Sanyal A, et al.

Antioxidants (Basel), 2023 Mar 23;12(4).
PMID: 37107164 DOI: 10.3390/antiox12040787

Natural-based biomaterials play an important role in developing new products for medical applications, primarily in cutaneous injuries. A large panel of biomaterials with antioxidant properties has revealed an advancement in supporting and expediting tissue regeneration. However, their low bioavailability in preventing cellular oxidative stress through the delivery system limits their therapeutic activity at the injury site. The integration of antioxidant compounds in the implanted biomaterial should be able to maintain their antioxidant activity while facilitating skin tissue recovery. This review summarises the recent literature that reported the role of natural antioxidant-incorporated biomaterials in promoting skin wound healing and tissue regeneration, which is supported by evidence from in vitro, in vivo, and clinical studies. Antioxidant-based therapies for wound healing have shown promising evidence in numerous animal studies, even though clinical studies remain very limited. We also described the underlying mechanism of reactive oxygen species (ROS) generation and provided a comprehensive review of ROS-scavenging biomaterials found in the literature in the last six years.
Diagnostic Challenge in Veterinary Pathology: Metastatic Mammary Tumor in a Female Tiger (Panthera Tigris)

Fraser C, Keong Kok M, Shameha Abdul Razak I, Puspitasari Y, Salleh A

Vet Pathol, 2024 Jan 21.
PMID: 38247139 DOI: 10.1177/03009858241226650
The Potential of Silver Nanoparticles for Antiviral and Antibacterial Applications: A Mechanism of Action

Salleh A, Naomi R, Utami ND, Mohammad AW, Mahmoudi E, Mustafa N, et al.

Nanomaterials (Basel), 2020 Aug 09;10(8).
PMID: 32784939 DOI: 10.3390/nano10081566

Rapid development of nanotechnology has been in high demand, especially for silver nanoparticles (AgNPs) since they have been proven to be useful in various fields such as medicine, textiles, and household appliances. AgNPs are very important because of their unique physicochemical and antimicrobial properties, with a myriad of activities that are applicable in various fields, including wound care management. This review aimed to elucidate the underlying mechanisms of AgNPs that are responsible for their antiviral properties and their antibacterial activity towards the microorganisms. AgNPs can be synthesized through three different methods-physical, chemical, and biological synthesis-as indicated in this review. The applications and limitations of the AgNPs such as their cytotoxicity towards humans and the environment, will be discussed. Based on the literature search obtained, the properties of AgNPs scrutinizing the antibacterial or antiviral effect shown different interaction towards bacteria which dependent on the synthesis processes followed by the morphological structure of AgNPs.
Fulltext Efficacy of Whole Cell Inactivated Vibrio harveyi Vaccine against Vibriosis in a Marine Red Hybrid Tilapia (Oreochromis niloticus × O. mossambicus) Model

Abu Nor N, Zamri-Saad M, Md Yasin IS, Salleh A, Mustaffa-Kamal F, Matori MF, et al.

Vaccines (Basel), 2020 Dec 04;8(4).
PMID: 33291587 DOI: 10.3390/vaccines8040734

Vibrio harveyi causes vibriosis in various commercial marine fish species. The infection leads to significant economic losses for aquaculture farms, and vaccination is an alternative approach for the prevention and control of fish diseases for aquaculture sustainability. This study describes the use of formalin-killed Vibrio harveyi (FKVh) strain Vh1 as a vaccine candidate to stimulate innate and adaptive immunities against vibriosis in a marine red hybrid tilapia model. Tilapia are fast growing; cheap; resistant to diseases; and tolerant to adverse environmental conditions of fresh water, brackish water, and marine water and because of these advantages, marine red hybrid tilapia is a suitable candidate as a model to study fish diseases and vaccinations against vibriosis. A total of 180 healthy red hybrid tilapias were gradually adapted to the marine environment before being divided into two groups, with 90 fish in each group and were kept in triplicate with 30 fish per tank. Group 1 was vaccinated intraperitoneally with 100 µL of FKVh on week 0, and a booster dose was similarly administered on week 2. Group 2 was similarly injected with PBS. Skin mucus, serum, and gut lavage were collected weekly for enzyme-linked immunosorbent assay (ELISA) and a lysozyme activity assay from a total of 30 fish of each group. On week 4, the remaining 60 fish of Groups 1 and 2 were challenged with 108 cfu/fish of live Vibrio harveyi. The clinical signs were monitored while the survival rate was recorded for 48 h post-challenge. Vaccination with FKVh resulted in a significantly (p < 0.05) higher rate of survival (87%) compared to the control (20%). The IgM antibody titer and lysozyme activities of Group 1 were significantly (p < 0.05) higher than the unvaccinated Groups 2 in most weeks throughout the experiment. Therefore, the intraperitoneal exposure of marine red hybrid tilapia to killed V. harveyi enhanced the resistance and antibody response of the fish against vibriosis.
The influence of feeding low and high level of Brachiaria decumbens diets on the hematology, serum biochemistry, and acute phase proteins of sheep

Muniandy KV, Chung ELT, Jaapar MS, Hamdan MHM, Reduan MFH, Salleh A, et al.

Trop Anim Health Prod, 2021 Jun 25;53(3):372.
PMID: 34173068 DOI: 10.1007/s11250-021-02820-1

The present study aims to determine the hematology, serum biochemistry, and acute phase proteins (APPs) responses of both serum and cerebrospinal fluid (CSF) in sheep fed with low and high levels of Brachiaria decumbens (B. decumbens) diets at different time phases. A total of 30 6-month-old male Dorper cross sheep were randomly divided into three treatment groups consisted of 10 sheep each. Treatment 1 (control) sheep were fed with Pennisetum purpureum and concentrates as the basal diet, whereas Treatments 2 and 3 sheep were fed with low (10%) and high (60%) level of B. decumbens, respectively. The hematology results revealed that there were significant differences (p
Effects of Pollination by the Indo-Malaya Stingless Bee (Hymenoptera: Apidae) on the Quality of Greenhouse-Produced Rockmelon

Azmi WA, Wan Sembok WZ, Yusuf N, Mohd Hatta MF, Salleh AF, Hamzah MAH, et al.

J Econ Entomol, 2019 02 12;112(1):20-24.
PMID: 30277528 DOI: 10.1093/jee/toy290

Rockmelon (Cucumis melo Linnaeus (Cucurbitales: Cucurbitaceae)) is a novel commercialized fruit in Malaysia and has great potential to become an important horticultural crop for the international market. In this study, we investigated the effects of pollination by the Indo-Malaya stingless bee Heterotrigona itama Smith (Hymenoptera: Apidae) on measures of yield and quality of rockmelon cultivated in the greenhouse, compared with hand cross-pollination and self-pollination. Results showed that rockmelon produced from plants pollinated by stingless bees and hand cross-pollination had higher fruit set, were heavier and larger, and contained higher numbers of seed per fruit compared with those produced by self-pollination. Pollination by stingless bees produced fruit with greater sweetness than either hand cross-pollination or self-pollination. This study demonstrated that stingless bee pollination produced rockmelon fruit of similar quality, but better yields compared to the other pollination treatments. We showed that stingless bees should be considered as an alternative, effective pollinator for the improved production of high quality rockmelon in commercial greenhouse cultivation.
Evaluating the Intestinal Immunity of Asian Seabass (Lates calcarifer, Bloch 1790) following Field Vaccination Using a Feed-Based Oral Vaccine

Raju T, Manchanayake T, Danial A, Zamri-Saad M, Azmai MNA, Md Yasin IS, et al.

Vaccines (Basel), 2023 Mar 06;11(3).
PMID: 36992186 DOI: 10.3390/vaccines11030602

This study describes the levels of gut lysozyme and IgM, the number, size and density of gut-associated lymphoid tissue (GALT) regions, and the lymphocyte population in Asian seabass following field oral administration of a feed-based vaccine. Fish in a grow-out farm were selected and divided into two groups; Group 1 was vaccinated at week 0, 2, and 6, while Group 2 was not vaccinated. Samplings were done at 2-week intervals when the fish were observed for clinical signs, and gross lesions were recorded. The intestinal tissue and gut lavage fluid were collected. GALT regions (numbers, size, density and population of lymphocytes) were analyzed. Clinical signs such as abnormal swimming pattern and death, and gross lesions including scale loss, ocular opacity, and skin ulceration were observed in both groups. At the end of the study, the incidence rate between both groups were significantly different (p < 0.05). The gut IgM level and lysozyme activity, lymphocyte population, number, size and density of GALT regions of Group 1 were significantly (p < 0.05) higher than Group 2. Therefore, this study concludes that the feed-based vaccine reduces the incidence of vibriosis by stimulating the gut immunity of the vaccinated fish with an enhanced GALT region, specific IgM production against Vibrio harveyi, and lysozyme responses.
Fulltext Co-Infections of Tilapia Lake Virus, Aeromonas hydrophila and Streptococcus agalactiae in Farmed Red Hybrid Tilapia

Basri L, Nor RM, Salleh A, Md Yasin IS, Saad MZ, Abd Rahaman NY, et al.

Animals (Basel), 2020 Nov 18;10(11).
PMID: 33217902 DOI: 10.3390/ani10112141

A high death rate among red hybrid tilapias was observed in a farm in Selangor, Malaysia, in January 2020. The affected fish appeared lethargic, isolated from schooling group, showed loss of appetite, red and haemorrhagic skin, exophthalmia and enlarged gall bladders. Histopathological assessment revealed deformation of kidney tubules, and severe congestion with infiltrations of inflammatory cells in the brains and kidneys. Syncytial cells and intracytoplasmic inclusion bodies were occasionally observed in the liver and brain sections. Tilapia Lake Virus (TiLV), Aeromonas hydrophila and Streptococcus agalactiae were identified in the affected fish, either through isolation or through PCR and sequencing analysis. The phylogenetic tree analysis revealed that the TiLV strain in this study was closely related to the previously reported Malaysian strain that was isolated in 2019. On the other hand, A. hydrophila and S. agalactiae were closer to Algerian and Brazilian strains, respectively. The multiple antibiotic resistance index for A. hydrophila and S. agalactiae was 0.50 and 0.25, respectively. Co-infections of virus and bacteria in cultured tilapia is a new threat for the tilapia industry.
Fulltext Evaluation of Chondroprotective Activity of Channa striatus in Rabbit Osteoarthritis Model

Abdul Kadir A, Abdul Kadir A, Abd Hamid R, Mat Jais AM, Omar J, Sadagatullah AN, et al.

Biomed Res Int, 2019;2019:6979585.
PMID: 31355276 DOI: 10.1155/2019/6979585

Objectives: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model.
Design: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined.
Results: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group.
Conclusion: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.
Immuno-protective efficiency of feed-based whole-cell inactivated bivalent vaccine against Streptococcus and Aeromonas infections in red hybrid tilapia (Oreochromis niloticus × Oreochromis mossambicus)

Monir MS, Yusoff MSM, Zulperi ZM, Hassim HA, Zamri-Saad M, Amal MNA, et al.

Fish Shellfish Immunol, 2021 Jun;113:162-175.
PMID: 33857622 DOI: 10.1016/j.fsi.2021.04.006

Streptococcosis and motile aeromonad septicemia (MAS) are well-known diseases in tilapia culture, which cause mass mortality with significant economic losses. The development of feed-based bivalent vaccines in controlling these diseases has been initiated, however, the mechanisms of immunities and cross-protection in fish remain unclear. This study was conducted to assess the immuno-protective as well as the cross-protective efficacy of a newly developed feed-based bivalent vaccine against Streptococcus and Aeromonas infections in red hybrid tilapia. A total of five groups of fish were vaccinated orally through two different techniques; bivalent vaccine (inactivated Streptococcus iniae and Aeromonas hydrophila) sprayed on feed pellets (BS group); bivalent vaccine (inactivated S. iniae and A. hydrophila) incorporated in feed (BI group); monovalent inactivated S. iniae and A. hydrophila vaccine separately incorporated into feed as monovalent S. iniae (MS group) and monovalent A. hydrophila (MA group); and control group (without vaccine). The feed-based vaccine was delivered orally at 5% of body weight for five consecutive days. The booster doses were given in the same manner on weeks 2 and 6. Serum and skin mucus samples were collected to assess the IgM responses using indirect ELISA. The first administration of the feed-based vaccine stimulated the IgM levels that lasted until week 3, while the second booster ensured that the IgM levels remained high for a period of 16 weeks in the BI, MS and MA groups. The BI group developed a strong and significantly (P
Fulltext The Impact of Feed Supplementations on Asian Buffaloes: A Review

Mohd Azmi AF, Ahmad H, Mohd Nor N, Goh YM, Zamri-Saad M, Abu Bakar MZ, et al.

Animals (Basel), 2021 Jul 07;11(7).
PMID: 34359160 DOI: 10.3390/ani11072033

With the increase in the global buffalo herd, the use of supplementation in the ruminant feeding has become an important area for many researchers who are looking for an isocaloric and isonitrogenous diet to improve production parameters. In order to improve the performance of the Asian water buffalo, the optimal balance of all nutrients, including energy and protein, are important as macronutrients. Dietary supplementation is one of the alternatives to enhance the essential nutrient content in the buffalo diet and to improve the rumen metabolism of the animal. Researchers have found that supplementation of concentrate and rumen bypass fat could change growth performance and carcass traits without causing any adverse effects on the buffalo growth. Some studies showed that dry matter intake, body condition score and some blood parameters and hormones related to growth responded positively to concentrate and rumen bypass fat supplementation. In addition, changes of feeding management by adding the supplement to the ruminant basal diet helped to increase the profit of the local farmers due to the increased performance and productivity of the animals. Nevertheless, the effects of dietary supplementation on the performance of ruminants are inconsistent. Thus, its long-term effects on the health and productivity of buffaloes still need to be further investigated.
Fulltext Dynamic tracking of human umbilical cord mesenchymal stem cells (hUC-MSCs) following intravenous administration in mice model

Chin SP, Marzuki M, Tai L, Mohamed Shahrehan NA, Ricky C, Fanty A, et al.

Regen Ther, 2024 Mar;25:273-283.
PMID: 38314402 DOI: 10.1016/j.reth.2024.01.003

INTRODUCTION: In the past decades, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have sparked interest in cellular therapy due to their immunomodulatory properties. Nevertheless, the fate of hUC-MSCs in the body remains poorly understood. This study aimed to investigate the biodistribution, homing and clearance of systemically administered hUC-MSCs in healthy BALB/c mice model.
METHODS: hUC-MSCs were labelled with GFP-Luc2 protein, followed by characterisation with flow cytometry. Upon intravenous infusion of transduced hUC-MSCs into the healthy BALB/c mice, the cells were dynamically monitored through the bioluminescent imaging (BLI) approach.
RESULTS: Transduction of hUC-MSCs with GFP-Luc2 not only preserved the characteristics of MSCs, but also allowed live monitoring of transduced cells in the mice model. Upon systemic administration, BLI showed that transduced hUC-MSCs first localised predominantly in the lungs of healthy BALB/c mice and mainly remained in the lungs for up to 3 days before eventually cleared from the body. At terminal sacrifice, plasma chemistry biomarkers remained unchanged except for C-peptide levels, which were significantly reduced in the hUC-MSCs group. Histopathological findings further revealed that hUC-MSCs infusion did not cause any adverse effects and toxicity to lung, liver and heart tissues.
CONCLUSIONS: Collectively, systemically administrated hUC-MSCs was safe and demonstrated dynamic homing capacity before eventually disappearing from the body.
A cross-sectional study of Angiostrongylus malaysiensis in rats and gastropod hosts from recreational parks in Kuala Lumpur, Malaysia: Detection, risk factors and pathology

Low SY, Lau SF, Ahmad NI, Sharma RSK, Rosli MZ, Mohd-Taib FS, et al.

Zoonoses Public Health, 2023 Nov;70(7):636-646.
PMID: 37403513 DOI: 10.1111/zph.13072

Angiostrongylus malaysiensis is a potential zoonotic parasite, which reported to co-occur with A. cantonensis in human cerebrospinal fluid. It is a heteroxenous nematode that primarily develops through the early larval stages in gastropods and attains sexual maturity within rats. This study was conducted to determine the host species responsible for the reservoir of A. malaysiensis and investigate the risk factor for transmission among the hosts in Kuala Lumpur, Malaysia. Sampling was conducted in six recreational parks. The rats were trapped alive using steel wire traps with bait, while the gastropods were collected by active searching. The rats were euthanized and dissected to collect any adult worms observed. The molecular detection of A. malaysiensis was performed by PCR on gastropod tissue samples. Biotic and landscape factors were recorded for risk factor analysis. In total, 82 rats and 330 gastropods were collected throughout the study. Overall, 3.64% of gastropods and 32.9% of rats were infected with A. malaysiensis. Rattus tiomanicus (Malayan wood rat) and Parmarion martensi (Yellow-shelled semi-slug) were found as important hosts for A. malaysiensis. Host species, sampling site and macrohabitat type are risk factors associated with the prevalence of A. malaysiensis infection in rats. For gastropods, host species and sampling site are risk factors that correlate with the parasite detection. In total, 128 adult A. malaysiensis were recovered from the infected rats. The mean intensity of infection with adult A. malaysiensis was 4.65 for Rattus rattus complex and 4.90 for R. tiomanicus. Adult worms were found in the pulmonary artery or right ventricle, while eggs and first-stage larvae were found in capillaries of the caudal lung lobe. Infected lungs showed extravasated red blood cells in the alveolar spaces. The pulmonary arteries in the infected lung lobe were thickened. Kepong Metropolitan Park is the hotspot area for A. malaysiensis in Kuala Lumpur. These results provide essential information for public health officials to develop targeted interventions to reduce the transmission of A. malaysiensis in urban areas, particularly in recreational parks.

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