Displaying publications 1 - 20 of 239 in total

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  1. Fulltext Low-Temperature Nitrogen Doping of Nanocrystalline Graphene Films with Tunable Pyridinic-N and Pyrrolic-N by Cold-Wall Plasma-Assisted Chemical Vapor Deposition
    Zainal Ariffin NH, Mohammad Haniff MAS, Syono MI, Ambri Mohamed M, Hamzah AA, Hashim AM
    ACS Omega, 2021 Sep 21;6(37):23710-23722.
    PMID: 34568651 DOI: 10.1021/acsomega.1c01520
    We report a viable method to produce nanocrystalline graphene films on polycrystalline nickel (Ni) with enhanced N doping at low temperatures by a cold-wall plasma-assisted chemical vapor deposition (CVD) method. The growth of nanocrystalline graphene films was carried out in a benzene/ammonia/argon (C6H6/NH3/Ar) system, in which the temperature of the substrate heated by Joule heating can be further lowered to 100 °C to achieve a low sheet resistance of 3.3 kΩ sq-1 at a high optical transmittance of 97.2%. The morphological, structural, and electrical properties and the chemical compositions of the obtained N-doped nanocrystalline graphene films can be tailored by controlling the growth parameters. An increase in the concentration of atomic N from 1.42 to 11.28 atomic percent (at.%) is expected due to the synergetic effects of a high NH3/Ar ratio and plasma power. The possible growth mechanism of nanocrystalline graphene films is also discussed to understand the basic chemical reactions that occur at such low temperatures with the presence of plasma as well as the formation of pyridinic-N- and pyrrolic-N-dominated nanocrystalline graphene. The realization of nanocrystalline graphene films with enhanced N doping at 100 °C may open great potential in developing future transparent nanodevices.
  2. Fulltext Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy
    Mohite P, Yadav V, Pandhare R, Maitra S, Saleh FM, Saleem RM, et al.
    ACS Omega, 2024 Feb 20;9(7):7277-7295.
    PMID: 38405458 DOI: 10.1021/acsomega.3c06501
    In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches. Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens. Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration. The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells. The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy.
  3. Fulltext Enhanced-Performance Triboelectric Nanogenerator Based on Polydimethylsiloxane/Barium Titanate/Graphene Quantum Dot Nanocomposites for Energy Harvesting
    Hatta FF, Mohammad Haniff MAS, Ambri Mohamed M
    ACS Omega, 2024 Feb 06;9(5):5608-5615.
    PMID: 38343971 DOI: 10.1021/acsomega.3c07952
    Triboelectric nanogenerators (TENGs) have been developed as promising energy-harvesting devices to effectively convert mechanical energy into electricity. TENGs use either organic or inorganic materials to initiate the triboelectrification process, followed by charge separation. In this study, a high-performance composite-based triboelectric nanogenerator (CTENG) device was fabricated, comprising polydimethylsiloxane (PDMS) as a polymeric matrix, barium titanite (BTO) nanopowders as dielectric fillers, and graphene quantum dots (GQDs) as conductive media. The PDMS/BTO/GQD composite film was prepared with GQDs doped into the mixture of PDMS/BTO and mechanically stirred. The composition of the GQD varied from 0 to 40 wt %. The composite was spin-coated onto flexible ITO on a PET sheet and dried in an oven at 80 °C for 24 h. The output performance of TENGs is enhanced by the increased concentration of 30 wt % GQD, which is 2 times higher than nanocomposite films without GQD. The PDMS/BTO/G30 TENG film depicted an increase in open-circuit voltage output (VOC), short-circuit current output (ISC), and power density reaching ∼310.0 V, ∼23.0 μA, and 1.6 W/m2, respectively. The simple and scalable process for the PDMS/BTO/GQD TENGs would benefit as a sustainable energy-harvesting system in small electronic devices.
  4. Correction to "Enhanced-Performance Triboelectric Nanogenerator Based on Polydimethylsiloxane/Barium Titanate/Graphene Quantum Dot Nanocomposites for Energy Harvesting"
    Hatta FF, Mohammad Haniff MAS, Ambri Mohamed M
    ACS Omega, 2024 Apr 09;9(14):16876.
    PMID: 38617648 DOI: 10.1021/acsomega.4c01247
    [This corrects the article DOI: 10.1021/acsomega.3c07952.].
  5. An ambient temperature stable and ready-to-use loop-mediated isothermal amplification assay for detection of toxigenic Vibrio cholerae in outbreak settings
    Engku Nur Syafirah EAR, Nurul Najian AB, Foo PC, Mohd Ali MR, Mohamed M, Yean CY
    Acta Trop, 2018 Jun;182:223-231.
    PMID: 29545156 DOI: 10.1016/j.actatropica.2018.03.004
    Cholera, caused by Vibrio cholerae is a foodborne disease that frequently reported in food and water related outbreak. Rapid diagnosis of cholera infection is important to avoid potential spread of disease. Among available diagnostic platforms, loop-mediated isothermal amplification (LAMP) is regarded as a potential diagnostic tool due to its rapidity, high sensitivity and specificity and independent of sophisticated thermalcycler. However, the current LAMP often requires multiple pipetting steps, hence is susceptible to cross contamination. Besides, the strict requirement of cold-chain during transportation and storage make its application in low resource settings to be inconvenient. To overcome these problems, the present study is aimed to develop an ambient-temperature-stable and ready-to-use LAMP assay for the detection of toxigenic Vibrio cholerae in low resource settings. A set of specific LAMP primers were designed and tested against 155 V. cholerae and non-V. cholerae strains. Analytical specifity showed that the developed LAMP assay detected 100% of pathogenic V. cholerae and did not amplified other tested bacterial strains. Upon testing against stool samples spiked with toxigenic V. cholerae outbreak isolates, the LAMP assay detected all of the spiked samples (n = 76/76, 100%), in contrast to the conventional PCR which amplified 77.6% (n = 59/76) of the tested specimens. In term of sensitivity, the LAMP assay was 100-fold more sensitive as compared to the conventional PCR method, with LOD of 10 fg per μL and 10 CFU per mL. Following lyophilisation with addition of lyoprotectants, the dry-reagent LAMP mix has an estimated shelf-life of 90.75 days at room temperature.
  6. Fusion of HSP70 gene of Mycobacterium tuberculosis to hemagglutinin (H5) gene of avian influenza virus in DNA vaccine enhances its potency
    Rasoli M, Omar AR, Aini I, Jalilian B, Syed Hassan SH, Mohamed M
    Acta Virol., 2010;54(1):33-9.
    PMID: 20201612
    A series of plasmids containing the HSP70 gene of Mycobacterium tuberculosis fused to the hemagglutinin (H5) gene of H5N1 avian influenza virus (AIV) (H5-HSP70 (heat shock protein 70) vaccine) or individual H5 gene (H5 vaccine) or HSP70 gene (HSP70 vaccine) were constructed based on the plasmid pcDNA3.1. Expression of H5 gene in Vero cells in vitro and in chickens in vivo was confirmed following their transfection and immunization with H5 or H5-HSP70 vaccines. Controls consisted of HSP70 vaccine, empty plasmid pcDNA3.1 and co-administered H5 and HSP70 vaccines. H5-HSP70 vaccine produced in chicken higher hemagglutination inhibition (HI) antibody titer than H5 vaccine. However, the increase was not statistically significant. We have demonstrated for the first time that the H5 DNA vaccine with fused HSP70 gene may produce an enhanced induction of humoral immune response to AIV in chickens.
  7. Fulltext Correction to: Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries
    Fulcher GR, Akhtar S, Al-Jaser SJ, Medina J, Mohamed M, Nicodemus NA, et al.
    Adv Ther, 2023 Jan;40(1):389-390.
    PMID: 36315342 DOI: 10.1007/s12325-022-02349-1
  8. Histological changes in male accessory reproductive organs in rats exposed to cigarette smoke and the protective effect of honey supplementation
    Mohamed M, Sulaiman SA, Jaafar H
    Afr J Tradit Complement Altern Med, 2012;9(3):329-35.
    PMID: 23983363
    The effect of cigarette smoke (CS) on histology of male accessory reproductive organs and the possible protective effect of honey supplementation in rats were investigated in this study. Rats received distilled water, honey, CS exposure or honey plus CS exposure. Honey (1.2 g/kg body weight/day) was administered by gavage and CS exposure (3 times per day) was done in a chamber for 13 weeks. CS exposure significantly increased relative weight of epididymis and ventral prostate. There were also significantly increased number of clear cells and epithelial height of cauda epididymis as well as severe interstitial oedema and decreased epithelial height of prostate gland. However, with the supplementation of honey, these histological changes were significantly reversed suggesting the protective effect of honey against the toxic effect of CS on male accessory reproductive organs in rats.
  9. Studies on the antioxidant properties of Tualang honey of Malaysia
    Mohamed M, Sirajudeen K, Swamy M, Yaacob NS, Sulaiman SA
    Afr J Tradit Complement Altern Med, 2009 Oct 15;7(1):59-63.
    PMID: 21304614
    Honey has been used since ancient times for its nutritional as well as curative properties. Tualang honey is collected from wild honey bees' hives on Tualang trees found in the Malaysian rain forest. It has been used traditionally for the treatment of various diseases, where its therapeutic value has partly been related to its antioxidant properties. This study therefore assessed the colour intensity, total phenolic content, antioxidant activity and antiradical activity of gamma irradiated Tualang Honey. The colour intensity at ABS₄₅₀ was 489.5 ± 1.7 mAU, total phenolic content was 251.7 ± 7.9 mg (gallic acid) /Kg honey, total antioxidant activity by FRAP assay was 322.1 ± 9.7 (µM Fe(II)) and the antiradical activity by DPPH assay was 41.30 ± 0.78 (% inhibition). The data confirms that the antioxidant properties of gamma irradiated Tualang honey are similar to other types of honeys reported in the literature.
  10. Fulltext Epidemiology of Male Sexual Dysfunction in Asian and European Regions: A Systematic Review
    Irfan M, Hussain NHN, Noor NM, Mohamed M, Sidi H, Ismail SB
    Am J Mens Health, 2020 7 7;14(4):1557988320937200.
    PMID: 32623948 DOI: 10.1177/1557988320937200
    Male sexual dysfunctions (MSDs) often remain undiagnosed and untreated in Asia compared to Europe due to conservative cultural and religious beliefs, socioeconomic conditions, and lack of awareness. There is a tendency for the use of traditional medicines and noncompliance with and reduced access to modern healthcare. The present systematic review compared the incidence and factors of MSD in European and Asian populations. English language population/community-based original articles on MSDs published in MEDLINE from 2008 to 2018 were retrieved. A total of 5392 studies were retrieved, of which 50 (25 Asian and 25 European) were finally included in this review. The prevalence of erectile dysfunction (ED) (0%-95.0% vs. 0.9%-88.8%), low satisfaction (3.2%-37.6% vs. 4.1%-28.3%), and hypoactive sexual desire disorder (HSDD) (0.7%-81.4 vs. 0%-65.5%) was higher in Asian than in European men, whereas the prevalence of anorgasmia (0.4% vs. 3%-65%) was lower in Asian than in European men. Age was an independent positive factor of MSD. In European men over 60 years old, the prevalence of premature ejaculation (PE) decreased. The prevalence of MSD was higher in questionnaires than in interviews. The significant factors were age, single status, low socioeconomic status, poor general health, less physical activity, cardiovascular diseases, diabetes, obesity, lower urinary tract symptoms, prostatitis, anxiety, depression and alcohol, tobacco, and drug use. The prevalence of MSD differed slightly in Asian and European men. There is a need to conduct large studies on the various Asian populations for the effective management of MSD.
  11. Fulltext Bee bread mitigates downregulation of steroidogenic genes, decreased spermatogenesis, and epididymal oxidative stress in male rats fed with high-fat diet
    Suleiman JB, Abu Bakar AB, Noor MM, Nna VU, Othman ZA, Zakaria Z, et al.
    Am J Physiol Endocrinol Metab, 2021 Sep 01;321(3):E351-E366.
    PMID: 34229480 DOI: 10.1152/ajpendo.00093.2021
    The pituitary-gonadal axis plays an important role in steroidogenesis and spermatogenesis, and by extension, fertility. The aim of this study was to investigate the protective role of bee bread, a natural bee product, against obesity-induced decreases in steroidogenesis and spermatogenesis. Thirty-two adult male Sprague-Dawley rats weighing between 200 and 300 g were divided into four groups (n = 8/group), namely: normal control (NC), high-fat diet (HFD), HFD plus bee bread administered concurrently for 12 wk (HFD + B), HFD plus orlistat administered concurrently for 12 wk (HFD + O) groups. Bee bread (0.5 g/kg) or orlistat (10 mg/kg/day) was suspended in distilled water and given by oral gavage daily for 12 wk. Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and adiponectin, as well as sperm count, motility, viability, normal morphology, and epididymal antioxidants decreased, whereas levels of leptin, malondialdehyde, and sperm nDNA fragmentation increased significantly in the HFD group relative to the NC group. There were significant decreases in the testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme, 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD in the testes of the HFD group. Furthermore, mount, intromission and ejaculatory latencies increased, and penile cGMP level decreased significantly in the HFD group. Supplementation with bee bread significantly reduced leptin level and increased adiponectin level, enhanced sperm parameters and reduced sperm nDNA fragmentation, upregulated the levels of steroidogenic genes and proteins in HFD-induced obese male rats. Bee bread improved steroidogenesis and spermatogenesis by upregulating steroidogenic genes. Therefore, bee bread may be considered as a potential supplementation to protect against infertility in overweight men or men with obesity.NEW & NOTEWORTHY The high-fat diet utilized in the present study induced obesity in the male rats. Bee bread supplementation mitigated impaired steroidogenesis, spermatogenesis, mating behavior, and fertility potential by counteracting the downregulation of steroidogenic genes, thus increasing testosterone levels and suppressing epididymal oxidative stress. These benefits may be due to the abundance of phenolic and flavonoid compounds in bee bread.
  12. Development of multiplex loop mediated isothermal amplification (m-LAMP) label-based gold nanoparticles lateral flow dipstick biosensor for detection of pathogenic Leptospira
    Nurul Najian AB, Engku Nur Syafirah EA, Ismail N, Mohamed M, Yean CY
    Anal Chim Acta, 2016 Jan 15;903:142-8.
    PMID: 26709307 DOI: 10.1016/j.aca.2015.11.015
    In recent years extensive numbers of molecular diagnostic methods have been developed to meet the need of point-of-care devices. Efforts have been made towards producing rapid, simple and inexpensive DNA tests, especially in the diagnostics field. We report on the development of a label-based lateral flow dipstick for the rapid and simple detection of multiplex loop-mediated isothermal amplification (m-LAMP) amplicons. A label-based m-LAMP lateral flow dipstick assay was developed for the simultaneous detection of target DNA template and a LAMP internal control. This biosensor operates through a label based system, in which probe-hybridization and the additional incubation step are eliminated. We demonstrated this m-LAMP assay by detecting pathogenic Leptospira, which causes the re-emerging disease Leptospirosis. The lateral flow dipstick was developed to detect of three targets, the LAMP target amplicon, the LAMP internal control amplicon and a chromatography control. Three lines appeared on the dipstick, indicating positive results for all representative pathogenic Leptospira species, whereas two lines appeared, indicating negative results, for other bacterial species. The specificity of this biosensor assay was 100% when it was tested with 13 representative pathogenic Leptospira species, 2 intermediate Leptospira species, 1 non-pathogenic Leptospira species and 28 other bacteria species. This study found that this DNA biosensor was able to detect DNA at concentrations as low as 3.95 × 10(-1) genomic equivalent ml(-1). An integrated m-LAMP and label-based lateral flow dipstick was successfully developed, promising simple and rapid visual detection in clinical diagnostics and serving as a point-of-care device.
  13. Development of a thermostabilised triplex LAMP assay with dry-reagent four target lateral flow dipstick for detection of Entamoeba histolytica and non-pathogenic Entamoeba spp
    Foo PC, Chan YY, Mohamed M, Wong WK, Nurul Najian AB, Lim BH
    Anal Chim Acta, 2017 May 08;966:71-80.
    PMID: 28372729 DOI: 10.1016/j.aca.2017.02.019
    This study highlighted the development of a four target nitrocellulose-based nucleic acid lateral flow immunoassay biosensor in a dry-reagent strip format for interpretation of double-labelled double-stranded amplicons from thermostabilised triplex loop-mediated isothermal amplification assay. The DNA biosensor contained two test lines which captured biotin and texas red labelled amplicons; a LAMP internal amplification control line that captured digoxigenin labelled amplicon; and a chromatography control line that validated the functionality of the conjugated gold nanoparticles and membrane. The red lines on detection pad were generated when the gold nanoparticles conjugated antibody bound to the fluorescein labelled amplicons, and the capture agents bound to their specific hapten on the other 5' end of the double-stranded amplicon. The applicability of this DNA biosensor was demonstrated using amoebiasis-causing Entamoeba histolytica simultaneously with the non-pathogenic but morphologically identical Entamoeba dispar and Entamoeba moshkovskii. The biosensor detection limit was 10 E. histolytica trophozoites, and revealed 100% specificity when it was evaluated against 3 medically important Entamoeba species and 75 other pathogenic microorganisms. Heat stability test showed that the biosensor was stable for at least 181 days at ambient temperature. This ready-to-use and cold-chain-free biosensor facilitated the post-LAMP analysis based on visualisation of lines on strip instead of observation of amplicon patterns in agarose gel.
  14. Effect of different doses of Malaysian honey on reproductive parameters in adult male rats
    Mohamed M, Sulaiman SA, Jaafar H, Sirajudeen KN
    Andrologia, 2012 May;44 Suppl 1:182-6.
    PMID: 21592175 DOI: 10.1111/j.1439-0272.2010.01159.x
    The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats.
  15. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress
    Haron MN, Mohamed M
    Andrologia, 2016 Jun;48(5):525-31.
    PMID: 26289766 DOI: 10.1111/and.12473
    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring.
  16. Fulltext Malaysian propolis and metformin mitigate subfertility in streptozotocin-induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour
    Nna VU, Bakar ABA, Ahmad A, Umar UZ, Suleiman JB, Zakaria Z, et al.
    Andrology, 2020 05;8(3):731-746.
    PMID: 31816190 DOI: 10.1111/andr.12739
    BACKGROUND: Diabetes mellitus is one of the risk factors for male subfertility/infertility. Malaysian propolis is reported to decrease hyperglycaemia in diabetic state.

    OBJECTIVES: The present study investigated the protective effect of Malaysian propolis on diabetes-induced subfertility/infertility. Additionally, its combined beneficial effects with metformin were investigated.

    MATERIALS AND METHODS: Forty adult male Sprague Dawley rats were randomly assigned into five groups, namely normal control, diabetic control, diabetic + Malaysian propolis (300 mg/k.g. b.w.), diabetic + metformin (300 mg/kg b.w.) and diabetic + Malaysian propolis + metformin. Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.) and treatment lasted for 4 weeks. During the 4th week, mating behavioural experiments were performed using sexually receptive female rats. Thereafter, fertility parameters were assessed in the female rats.

    RESULTS: Malaysian propolis increased serum and intratesticular free testosterone levels, up-regulated the mRNA levels of AR and luteinizing hormone receptor, up-regulated the mRNA and protein levels of StAR, CYP11A1, CYP17A1, 3β-HSD and 17β-HSD in the testes of diabetic rats. Furthermore, Malaysian propolis up-regulated testicular MCT2, MCT4 and lactate dehydrogenase type C mRNA levels, in addition to improving sperm parameters (count, motility, viability and normal morphology) and decreasing sperm nDNA fragmentation in diabetic rats. Malaysian propolis improved mating behaviour by increasing penile guanosine monophosphate levels. Malaysian propolis also improved fertility outcome as seen with decreases in pre- and post-implantation losses, increases in gravid uterine weight, litter size per dam and foetal weight. Malaysian propolis's effects were comparable to metformin. However, their combination yielded better results relative to the monotherapeutic interventions.

    CONCLUSION: Malaysian propolis improves fertility potential in diabetic state by targeting steroidogenesis, testicular lactate metabolism, spermatogenesis and mating behaviour, with better effects when co-administered with metformin. Therefore, Malaysian propolis shows a promising complementary effect with metformin in mitigating Diabetes mellitus-induced subfertility/infertility.

  17. Orlistat attenuates obesity-induced decline in steroidogenesis and spermatogenesis by up-regulating steroidogenic genes
    Suleiman JB, Nna VU, Othman ZA, Zakaria Z, Bakar ABA, Mohamed M
    Andrology, 2020 09;8(5):1471-1485.
    PMID: 32438512 DOI: 10.1111/andr.12824
    BACKGROUND: Steroidogenesis decline is reported to be one of the mechanisms associated with obesity-induced male factor subfertility/infertility.

    OBJECTIVES: We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity-induced steroidogenesis and spermatogenesis decline.

    MATERIALS AND METHODS: Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control, high-fat diet, high-fat diet plus orlistat preventive group and high-fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high-fat diet for 12 weeks (high-fat diet plus orlistat preventive group) or administered from week 7-12 post- high-fat diet feeding (high-fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses.

    RESULTS: Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra-testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased in the testes of the high-fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high-fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high-fat diet-induced obese male rats, with the preventive group (high-fat diet plus orlistat preventive group) having better results relative to the treatment group (high-fat diet plus orlistat treatment group).

    DISCUSSION AND CONCLUSION: Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up-regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.

  18. Fulltext Down-regulation of steroidogenesis-related genes and its accompanying fertility decline in streptozotocin-induced diabetic male rats: ameliorative effect of metformin
    Nna VU, Bakar ABA, Ahmad A, Mohamed M
    Andrology, 2019 01;7(1):110-123.
    PMID: 30515996 DOI: 10.1111/andr.12567
    BACKGROUND: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged.

    OBJECTIVES: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats.

    MATERIALS AND METHODS: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks.

    RESULTS: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, as well as the level of StAR protein and activities of CYP11A1, 3β-HSD, and 17β-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre- and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome.

    DISCUSSION AND CONCLUSION: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state.

  19. Fulltext Composition of Royal Jelly (RJ) and Its Anti-Androgenic Effect on Reproductive Parameters in a Polycystic Ovarian Syndrome (PCOS) Animal Model
    Ab Hamid N, Abu Bakar AB, Mat Zain AA, Nik Hussain NH, Othman ZA, Zakaria Z, et al.
    Antioxidants (Basel), 2020 Jun 07;9(6).
    PMID: 32517356 DOI: 10.3390/antiox9060499
    Royal jelly (RJ) has been shown to contribute its positive effects upon imbalance in the reproductive system. However, it remains unknown as to whether RJ has an anti-androgenic effect on reproductive parameters in a polycystic ovarian syndrome (PCOS) animal model. Composition of RJ was assessed by phytochemical screening and the LC-MS method. Forty immature female rats (3 weeks, 40-50 g) were randomly divided into five groups (n = 8 per group), i.e., control, testosterone (T), T+100RJ (100 mg/kg/day), T+200RJ (200 mg/kg/day RJ), and T+400RJ (400 mg/kg/day RJ) groups. Hyperandrogenism was induced by daily subcutaneous injection of T propionate for 3 weeks, followed by oral RJ for 4 weeks. The T+200RJ group had a significantly higher follicle-stimulating hormone level, and significantly lower luteinizing hormone, testosterone, and estradiol levels in comparison to the T group. Malondialdehyde level and glutathione peroxidase activity were significantly lower, while total antioxidant capacity level was significantly higher in the T+200RJ group compared to the T group. Histologically, the T+200RJ group showed recovery of various stages of ovarian follicular development. RJ at 200 mg/kg/day for 4 weeks significantly improved reproductive parameters in PCOS rats partly due to its anti-androgenic effect through antioxidant action and probably due to modulation on estrogenic activity, which needs further study to evaluate its exact mechanism of action.
  20. Fulltext Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation
    Zakaria Z, Othman ZA, Suleiman JB, Che Jalil NA, Ghazali WSW, Nna VU, et al.
    Antioxidants (Basel), 2021 Dec 20;10(12).
    PMID: 34943134 DOI: 10.3390/antiox10122031
    Metabolic dysfunction-associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid closely linked with many metabolic disorders, oxidative stress and inflammation. We aimed to evaluate the hepatoprotective effect of bee bread on oxidative stress and inflammatory parameters in MAFLD rats. Twenty-eight male Sprague-Dawley rats were assigned into four groups (n = 7/group): normal control (NC), high-fat diet (HFD), bee bread (HFD + Bb, HFD + 0.5 g/kg/day bee bread) and orlistat (HFD + Or, HFD + 10 mg/kg/day orlistat) groups. After 12 weeks, the HFD group demonstrated significantly higher body weight gain, serum levels of lipids (TG, TC, LDL), liver enzymes (AST, ALT, ALP) and adiponectin, liver lipids (TG, TC) and insulin resistance (HOMA-IR). Furthermore, the HFD group showed significantly decreased antioxidant enzyme activities (GPx, GST, GR, SOD, CAT) and GSH level, and increased liver oxidative stress (TBARS, NO), translocation of Nrf2 to the nucleus, Keap1 expression and inflammation (TNF-α, NF-κβ, MCP-1) together with histopathological alterations (steatosis, hepatocyte hypertrophy, inflammatory cell infiltration, collagen deposition), which indicated the presence of non-alcoholic steatohepatitis (NASH) and fibrosis. Bee bread significantly attenuated all these changes exerted by HFD feeding. In conclusion, our results suggest that bee bread might have antioxidant, anti-inflammatory, anti-steatotic and anti-fibrotic effects that are beneficial in protecting liver progression towards NASH and fibrosis.
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