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Peptide inhibitors of Macrobrachium rosenbergii nodavirus

Thong QX, Wong CL, Ooi MK, Kueh CL, Ho KL, Alitheen NB, et al.

J Gen Virol, 2018 09;99(9):1227-1238.
PMID: 30041713 DOI: 10.1099/jgv.0.001116

Macrobrachium rosenbergii nodavirus (MrNv) causes white tail disease (WTD) in giant freshwater prawns, which leads to devastating economic losses in the aquaculture industry. Despite extensive research on MrNv, there is still no antiviral agent to treat WTD. Thus, the main aim of this study was to identify potential anti-MrNv molecules. A 12-mer phage-displayed peptide library was biopanned against the MrNv virus-like particle (VLP). After four rounds of biopanning, two dominant phages harbouring the amino acid sequences HTKQIPRHIYSA and VSRHQSWHPHDL were selected. An equilibrium binding assay in solution was performed to determine the relative dissociation constant (KDrel) of the interaction between the MrNv VLP and the selected fusion phages. Phage-HTKQIPRHIYSA has a KDrel value of 92.4±22.8 nM, and phage-VSRHQSWHPHDL has a KDrel value of 12.7±3.8 nM. An in-cell elisa was used to determine the inhibitory effect of the synthetic peptides towards the entry of MrNv VLP into Spodoptera frugiperda (Sf9) cells. Peptides HTKQIPRHIYSA and VSRHQSWHPHDL inhibited the entry of the MrNv VLP into Sf9 cells with IC50 values of 30.4±3.6 and 26.5±8.8 µM, respectively. Combination of both peptides showed a significantly higher inhibitory effect with an IC50 of 4.9±0.4 µM. An MTT assay revealed that the viability of MrNv-infected cells increased to about 97 % in the presence of both peptides. A real-time RT-PCR assay showed that simultaneous application of both peptides significantly reduced the number of MrNv per infected cell, from 97±9 to 11±4. These peptides are lead compounds which can be further developed into potent anti-MrNv agents.

Matched MeSH terms: Cell Survival/drug effects; Nodaviridae/drug effects*
An Overview on the Toxicological Properties of Ionic Liquids toward Microorganisms

Sivapragasam M, Moniruzzaman M, Goto M

Biotechnol J, 2020 Apr;15(4):e1900073.
PMID: 31864234 DOI: 10.1002/biot.201900073

Ionic liquids (ILs), a class of materials with unique physicochemical properties, have been used extensively in the fields of chemical engineering, biotechnology, material sciences, pharmaceutics, and many others. Because ILs are very polar by nature, they can migrate into the environment with the possibility of inclusion in the food chain and bioaccumulation in living organisms. However, the chemical natures of ILs are not quintessentially biocompatible. Therefore, the practical uses of ILs must be preceded by suitable toxicological assessments. Among different methods, the use of microorganisms to evaluate IL toxicity provides many advantages including short generation time, rapid growth, and environmental and industrial relevance. This article reviews the recent research progress on the toxicological properties of ILs toward microorganisms and highlights the computational prediction of various toxicity models.

Matched MeSH terms: Bacteria/drug effects; Fungi/drug effects
Fulltext Camel whey protein hydrolysates induced G2/M cellcycle arrest in human colorectal carcinoma

Murali C, Mudgil P, Gan CY, Tarazi H, El-Awady R, Abdalla Y, et al.

Sci Rep, 2021 03 29;11(1):7062.
PMID: 33782460 DOI: 10.1038/s41598-021-86391-z

Camel milk has been gaining immmense importance due to high nutritious value and medicinal properties. Peptides from milk proteins is gaining popularity in various therapeutics including human cancer. The study was aimed to investigate the anti-cancerous and anti-inflammatory properties of camel whey protein hydrolysates (CWPHs). CWPHs were generated at three temperatures (30 ℃, 37 ℃, and 45 ℃), two hydrolysis timepoints (120 and 360 min) and with three different enzyme concentrations (0.5, 1 and 2 %). CWPHs demonstrated an increase in anti-inflammatory effect between 732.50 (P-6.1) and 3779.16 (P-2.1) µg Dicolfenac Sodium Equivalent (DSE)/mg protein. CWPHs (P-4.3 & 5.2) inhibited growth of human colon carcinoma cells (HCT116) with an IC50 value of 231 and 221 μg/ml, respectively. P-4.3 induced G2/M cell cycle arrest and modulated the expression of Cdk1, p-Cdk1, Cyclin B1, p-histone H3, p21 and p53. Docking of two peptides (AHLEQVLLR and ALPNIDPPTVER) from CWPHs (P-4.3) identified Polo like kinase 1 as a potential target, which strongly supports our in vitro data and provides an encouraging insight into developing a novel peptide-based anticancer formulation. These results suggest that the active component, CWPHs (P-4.3), can be further studied and modeled to form a small molecule anti-cancerous therapy.

Matched MeSH terms: Cell Division/drug effects*; G2 Phase/drug effects*
Performance of Commercial Insecticide Formulations Against Different Developmental Stages of Insecticide-Resistant Tropical Bed Bugs (Hemiptera: Cimicidae)

Leong XY, Kim DY, Dang K, Singham GV, Doggett SL, Lee CY

J Econ Entomol, 2020 02 08;113(1):353-366.
PMID: 31586445 DOI: 10.1093/jee/toz266

This study examined the presence of insecticide resistance in different developmental stages (adults, first instars, and eggs) of the tropical bed bug, Cimex hemipterus (F.) using several insecticide formulations. Adults and first instars of five strains (Queensland, Kuala Lumpur, Bukit Mertajam, Saujana, and Krystal Point) were evaluated using the surface contact method and compared with a susceptible strain (Monheim) of the common bed bug Cimex lectularius L. The insecticide formulations were used at their label rates in this study: Tandem (thiamethoxam [11.6%], lambda-cyhalothrin [3.5%]) at 183.96 mg/m2; Temprid SC (imidacloprid [21%], beta-cyfluthrin [10.5%]) at 106.13 mg/m2; Sumithion 20CS (fenitrothion [20%]) at 250 mg/m2; Pesguard FG161 (d-tetramethrin [4.4%], cyphenothrin [13.2%]) at 110 mg/m2; and Sumithrin 10SEC (d-phenothrin [10%]) at 100 mg/m2. Results showed a very high level of resistance to Pesguard FG161 (388.3 to >605.0 times) and Sumithrin (302.9 to >365.5 times) in all adults of the strains tested, whereas low to high levels of resistance were registered for Tandem (1.4-4.7 times), Temprid (7.3-16.7 times), and Sumithion (1.2-14.6 times) for adults of all bed bug strains. For first instars, resistance to the former two formulations were high to very high (31.4-118.1 times). In contrast, they showed lower resistance to Tandem, Temprid, and Sumithion (1.0-10.2 times). An immersion method used to test on bed bug eggs found high to very high resistance toward all tested formulations. Results demonstrate that the resistance level varies between bed bug developmental stages.

Matched MeSH terms: Bedbugs/drug effects*; Insecticide Resistance/drug effects
Gonadotropin-inhibitory hormone mediates behavioral stress responses

Ubuka T, Parhar IS, Tsutsui K

Gen Comp Endocrinol, 2018 09 01;265:202-206.
PMID: 29510150 DOI: 10.1016/j.ygcen.2018.03.004

Gonadotropin-inhibitory hormone (GnIH) is an inhibitor of the hypothalamic-pituitary-gonadal (HPG) axis. GnIH is also called RFamide-related peptide (RFRP) as GnIH peptides have a characteristic C-terminal LPXRFiamide (X = L or Q) sequence. GnIH is thought to be the mediator of stress by negatively regulating the HPG axis as various stressors increase GnIH mRNA, GnIH peptide or GnIH neuronal activity. On the other hand, GnIH may also mediate behavioral stress responses as GnIH neuronal fibers and GnIH receptors are widely located in the limbic system of telencephalon, diencephalon and midbrain area. Previous studies have shown that intracerebroventricular (i.c.v.) administration of GnIH (RFRP) blocks morphine-induced analgesia in hot plate and formalin injection tests in rats suggesting that GnIH increases sensitivity to pain. GnIH (RFRP) also increases anxiety-like behavior in rats. RNA interference of GnIH gene (GnIH RNAi) increases locomotor activity of white-crowned sparrow and Japanese quail and i.c.v. administration of GnIH decreases GnIH RNAi induced locomotor activity. It was further shown that i.c.v. administration of GnIH (RFRP) decreases aggressive behavior in male quail and sexual behavior in male rats, female white-crowned sparrow and female hamsters. These results suggest that GnIH decreases threat to homeostasis of the organism by increasing pain sensitivity, anxiety and decreasing locomotor activity, aggressive behavior and sexual behavior. GnIH may also mediate the effect of stress on behavior.

Matched MeSH terms: Aggression/drug effects; Neurons/drug effects
The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism

Hairi HA, Shuid AN, Ibrahim N', Jamal JA, Mohamed N, Mohamed IN

Curr Drug Targets, 2019;20(2):192-200.
PMID: 28814228 DOI: 10.2174/1389450118666170816123740

BACKGROUND: Phytoestrogens have recently been claimed to positively influence menopausal discomforts, including hot flashes. However, little is known about the influence of phytoestrogens on core body temperature during oestrogen fluctuation at menopause.
OBJECTIVE: Previously published findings showed that phytoestrogens could relieve menopausal complaints, thus, the present review was aimed at assessing the effects of phytoestrogens on thermoregulatory mechanism during menopausal transition.
RESULTS: The molecular mechanisms underlying hot flashes are complex. Oestrogen fluctuations cause hypothalamic thermoregulatory centre dysfunction, which leads to hot flashes during menopause. The phytoestrogens of interest, in relation to human health, include isoflavones, lignans, coumestans, and stilbenes, which are widely distributed in nature. The phytoestrogens are capable of reducing hot flashes via their oestrogen-like hormone actions. The potential effects of phytoestrogens on hot flashes and their molecular mechanisms of action on thermoregulatory centre are discussed in this review.
CONCLUSION: The effects of phytoestrogens on these mechanisms may help explain their beneficial effects in alleviating hot flashes and other menopausal discomforts.

Matched MeSH terms: Body Temperature Regulation/drug effects; Menopause/drug effects*
Fulltext Status of insecticide resistance in An. culicifacies in Gadchiroli (Maharashtra) India

Chand G, Behera P, Bang A, Singh N

Pathog Glob Health, 2017 Oct;111(7):362-366.
PMID: 28971738 DOI: 10.1080/20477724.2017.1378836

An. culicifacies is the major vector of malaria in tribal community and tribal dominated areas in India. Development of resistance to insecticides is the major challenge to curb the transmission. Gadchiroli (Maharashtra) is a tribal district in central India where incidence of malaria increased from 2012 to 2015 despite indoor space spray with synthetic pyrethroids. To determine the susceptibility status of An. culicifacies against commonly used insecticides in public health program in Gadchiroli. standard WHO method and test kit were used. The insecticide impregnated papers were procured from vector control unit Malaysia. An. culicifacies found resistance to three major groups of pesticides i.e. organochlorine (DDT 4%), organophosphorous (Malathion 5%) and pyrethroids (Cyfluthrin 0.15%, Deltametherin 0.05% and Lambdacyhalothrin 0.05%). The susceptibility status in Permethrin 0.75% needs further confirmation. Development of resistance to different insecticides of varied groups is an adverse finding for the elimination of malaria, explaining the recent increase in malaria incidence in Gadchiroli. The phenomenon further needs to be studied in different locations and the susceptibility needs to test against other insecticides. The findings may have significant implications to the choice of insecticides in the malaria control program in tribal areas.

Matched MeSH terms: Anopheles/drug effects*; Insect Vectors/drug effects*
The Importance of Some Plant Extracts as Skin Anti-aging Resources: A Review

Yasin ZAM, Ibrahim F, Rashid NN, Razif MFM, Yusof R

Curr Pharm Biotechnol, 2017;18(11):864-876.
PMID: 29256348 DOI: 10.2174/1389201019666171219105920

BACKGROUND: Skin is the largest and most visible organ of the body. Many of its functions include temperature regulation, immunity from microorganisms, maintaining electrolyte balance, and protection from physical injuries, chemical agents and ultraviolet (UV) radiation. Aging occurs in every layer of the skin, primarily due to the degradation of its components. Induction of degradative enzymes and the abundant production of reactive oxygen species lead to skin aging. Understanding the complexity of skin structure and factors contributing to the skin aging will help us impede the aging process. Applications of anti-aging products are a common method to prevent or repair damages that lead to aging.
CONCLUSION: This review will provide information on the causes and indicators of skin aging as well as examine studies that have used plants to produce anti-aging products.

Matched MeSH terms: Skin Physiological Phenomena/drug effects; Skin Aging/drug effects*
Fulltext Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis

Puttarak P, Dilokthornsakul P, Saokaew S, Dhippayom T, Kongkaew C, Sruamsiri R, et al.

Sci Rep, 2017 09 06;7(1):10646.
PMID: 28878245 DOI: 10.1038/s41598-017-09823-9

Centella asiatica (L.) Urb. has been used as an herbal brain tonic for mental disorders and enhancing memory, but no review of the overall evidence of C. asiatica and cognitive function has been conducted. This study aims to determine the effects of C. asiatica on cognitive function and its related properties. The current systematic review includes five randomized controlled trials (RCTs) conducted to determine the effect of C. asiatica alone and six RCTs conducted to determine the effect of C. asiatica-containing products. Meta-analysis indicated that there are no significant differences in all cognitive function domains of C. asiatica when compared to placebo. However, it could improve mood by increasing alert scores [SMD: 0.71 (95% CI; 0.01 to 1.41); I2 = 30.5%] and decreasing anger scores at 1 hour after treatment [SMD: -0.81 (95%CI; -1.51 to -0.09); I2 = 36.6%]. None of the studies reported adverse effects of C. asiatica. In conclusion, there is not strong evidence to support the use of C. asiatica for cognitive function improvement in each cognitive domain. C. asiatica could improve alertness and relieve anger. However, some limitations should be aware including dose regimen, plant preparation, standardization, and product variation. Future well-designed clinical trials using suitable doses of standardized C. asiatica are still needed.

Matched MeSH terms: Affect/drug effects*; Cognition/drug effects*
Vasorelaxant effect of 5,7,4'- Trihydroxyflavanone (Naringenin) via endothelium dependent, potassium and calcium channels in Sprague Dawley rats: Aortic ring model

Tan CS, Tew WY, Jingying C, Yam MF

Chem Biol Interact, 2021 Oct 01;348:109620.
PMID: 34411564 DOI: 10.1016/j.cbi.2021.109620

Naringenin is a naturally occurring flavanone (flavonoid) known to have bioactive effects on human health. It has been reported to show cardiovascular effects. This study aimed to investigate the possible vasorelaxant effect of naringenin and the mechanism behind it by using a Sprague Dawley rat aortic ring assay model. Naringenin caused significant vasorelaxation of endothelium-intact aortic rings precontracted with phenylephrine (pD2 = 4.27 ± 0.05; Rmax = 121.70 ± 4.04%) or potassium chloride (pD2 = 4.00 ± 0.04; Rmax = 103.40 ± 3.82%). The vasorelaxant effect decreased in the absence of an endothelium (pD2 = 3.34 ± 0.10; Rmax = 62.29 ± 2.73%). The mechanisms of the vasorelaxant effect of naringenin in the presence of antagonists were also investigated. Indomethacin, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, atropine, 4-aminopyridine, Nω-nitro-l-arginine methyl ester, glibenclamide and propranolol significantly reduced the relaxation stimulated by naringenin in the presence of endothelium. Besides that, the effect of naringenin on the voltage-operated calcium channel (VOCC) in the endothelium-intact aortic ring was studied, as was intracellular Ca2+ release from the sarcoplasmic reticulum (SR) in the endothelium-denuded aortic ring. The results showed that naringenin also significantly blocked the entry of Ca2+ via the VOCC, SERCA/SOCC and suppressed the release of Ca2+ from the SR. Thus, the vasorelaxant effect shown by naringenin mostly involve the COX pathway, the endothelium-dependent pathway via NO/sGC/prostaglandin, calcium and potassium channels.

Matched MeSH terms: Aorta/drug effects; Vasodilation/drug effects
A starch/gelatin-based Halochromic film with black currant anthocyanin and Nanocellulose-stabilized cinnamon essential oil Pickering emulsion: Towards real-time Salmon freshness assessment

Lim HJ, Tang SY, Chan KW, Manickam S, Yu LJ, Tan KW

Int J Biol Macromol, 2024 Aug;274(Pt 1):133329.
PMID: 38908640 DOI: 10.1016/j.ijbiomac.2024.133329

Neoterically, food packaging systems designed solely for prolonging shelf life or monitoring freshness could not fulfil the dynamic demands of consumers. In this current investigation, using the solvent casting method, a versatile halochromic indicator was created by integrating black currant anthocyanin and cinnamon essential oil-loaded Pickering emulsion into a starch/gelatin matrix. The resulting indicator film underwent scrutiny for its structural, pH-sensitive, antioxidant, and antimicrobial attributes. Unexpectedly, the amalgamation of anthocyanin and essential oil led to decreased antioxidant activity, dropping from 73.23 ± 2.17 to 28.87 ± 2.50 mg Trolox equivalent/g sample. Additionally, no discernible antimicrobial properties were detected in the composite film sample against both Staphylococcus aureus and Escherichia coli. Fourier transform infrared analyses unveiled robust intermolecular interactions among the film-forming components, providing insights into the observed antagonistic effect. The indicator film displayed distinctive colour changes corresponding to the fresh (greyish-brown), onset of decomposition (khaki), and spoiled (dark green) stages of the stored fish sample. This highlights its promising potential for providing real-time indications of food spoilage. These findings are important for the efficient design of composite films incorporating anthocyanins and essential oils. They serve as a guide towards their potential use as multifunctional packaging materials in the food industry.

Matched MeSH terms: Escherichia coli/drug effects; Staphylococcus aureus/drug effects
Multi-omics reveal toxicity mechanisms underpinning nanoplastic in redclaw crayfish (Cherax quadricarinatus)

Zhu T, Yao C, Hong S, Song W, Zanuri NM, Lv W, et al.

Sci Total Environ, 2024 Nov 15;951:175680.
PMID: 39173758 DOI: 10.1016/j.scitotenv.2024.175680

We investigated the effects of different nanoplastic (NP, size = 100 nm) concentrations on red crayfish (Cherax quadricarinatus) and examined toxicity mechanisms. We established four concentration groups (control (CK): 0 μg/L; Low: 100 μg/L; Medium: 500 μg/L; and High: 1000 μg/L) and analyzed toxicity effects in C. quadricarinatus hepatopancreas using histopathological, transcriptomic, metabolomic, and fluorescence methods. NP exposure caused histological lesions and oxidative stress in hepatopancreas, and also significantly decreased glutathione (GSH) (P drug metabolism-cytochrome P450, and P53 signaling pathways. Metabolomic analyses indicated some metabolic processes were affected by NPs, including bile secretion, primary bile acid biosynthesis, and cholesterol metabolism. Caspase 3, 8, and 9 distribution levels in hepatopancreatic tissues were also determined by immunofluorescence; positive caspase staining increased with increased NP concentrations. Additionally, by examining relative Bcl-2, Bax, Apaf-1, and p53 mRNA expression levels, Bcl-2 expression was significantly decreased with increasing NP concentrations; and the expression of Bcl-2 was increasing significantly with the NPs concentration increasing. Bax expression in Low, Medium, and High groups was also significantly higher when compared with the CK group (P

Matched MeSH terms: Apoptosis/drug effects; Hepatopancreas/drug effects
Novel detoxifier of spironolactone against triptolide-induced hepatotoxicity through inhibition of RPB1 degradation

Qiang L, Lee SH, Xiao P, Chunhui L, Lei G, Shaoli C, et al.

J Ethnopharmacol, 2025 Jan 10;336:118722.
PMID: 39182704 DOI: 10.1016/j.jep.2024.118722

ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a major bioactive and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii (T. wilfordii) Hook F. It exhibits potent antitumor, immunosuppressive, and anti-inflammatory biological activities; however, its clinical application is hindered by severe systemic toxicity. Two preparations of T. wilfordii, including T. wilfordii glycoside tablets and T. wilfordii tablets, containing triptolide, are commonly used in clinical practice. However, their adverse side effects, particularly hepatotoxicity, limit their safe use. Therefore, it is crucial to discover potent and specific detoxification medicines for triptolide.
AIM OF THE STUDY: This study aimed to investigate the detoxification effects and potential mechanism of action of spironolactone on triptolide-induced hepatotoxicity to provide a potential detoxifying strategy for triptolide, thereby promoting the safe applications of T. wilfordii preparations in clinical settings.
MATERIALS AND METHODS: Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet staining. Nuclear fragmentation was visualized using 4',6-diamidino-2-phenylindole (DAPI) staining, and protein expression was analyzed by Western blotting. The inhibitory effect of spironolactone on triptolide-induced hepatotoxicity was evaluated by examining the effects of spironolactone on serum alanine aminotransferase and aspartate aminotransferase levels, as well as liver pathology in a mouse model of triptolide-induced acute hepatotoxicity. Furthermore, a survival assay was performed to investigate the effects of spironolactone on the survival rate of mice exposed to a lethal dose of triptolide. The effect of spironolactone on triptolide-induced global transcriptional repression was assessed through 5-ethynyl uridine staining.
RESULTS: Triptolide treatment decreased the cell viability, increased the nuclear fragmentation and the cleaved caspase-3 levels in both hepatoma cells and hepatocytes. It also increased the alanine aminotransferase and aspartate aminotransferase levels, induced the hepatocyte swelling and necrosis, and led to seven deaths out of 11 mice. The above effects could be mitigated by pretreatment with spironolactone. Additionally, molecular mechanism exploration unveiled that spironolactone inhibited triptolide-induced DNA-directed RNA polymerase II subunit RPB1 degradation, consequently increased the fluorescence intensity of 5-ethynyl uridine staining for nascent RNA.
CONCLUSIONS: This study shows that spironolactone exhibits a potent detoxification role against triptolide hepatotoxicity, through inhibition of RPB1 degradation induced by triptolide and, in turn, retardation of global transcriptional inhibition in affected cells. These findings suggest a potential detoxification strategy for triptolide that may contribute to the safe use of T. wilfordii preparations.

Matched MeSH terms: Cell Survival/drug effects; Liver/drug effects
Unveiling the anti-giardial properties of Andrographis paniculata leaf extract through in vitro studies

Haldar T, Sardar SK, Ghosal A, Das K, Saito-Nakano Y, Dutta S, et al.

Trop Biomed, 2024 Sep 01;41(3):319-327.
PMID: 39548787 DOI: 10.47665/tb.41.3.013

Giardiasis, caused by the parasite Giardia lamblia, is a prevalent and serious public health concern, particularly affecting children worldwide. The primary mode of transmission for the parasite is through contaminated food and water sources and often leads to the onset of diarrhoea in infected individuals. However, the present medications for Giardiasis treatment often come with numerous side effects, while the growing problem of drug resistance adds a significant complication. Therefore, there is an urgent need for alternative treatments. In this study, we explored the in-vitro potential of Andrographis paniculata leaf extract as a possible alternative treatment for Giardiasis. Our investigation involved assessing the impact of the ethanolic extract on Giardia trophozoites through the analysis of parameters such as cell death, morphological alterations, adherence, ROS generation, and cell cycle dynamics. A. paniculata leaf extracts demonstrated significant inhibitory activity against the growth of Giardia trophozoites. After being incubated for 24 hours, the test results revealed an IC50 value of 51.26µg/ml (95% CI 37.17- 65.35) for inducing cell death in Giardia trophozoites. We observed a substantial degradation of DNA, alteration in morphology, inhibition in adherence, ROS generation and inhibition of the cell cycle in Giardia trophozoites. The findings indicate that A. paniculata extract has the potential to be used as a therapeutic treatment for giardiasis. This approach aims to offer a natural therapeutic solution for giardiasis, minimizing side effects and reducing the risk of drug resistance.

Matched MeSH terms: Cell Cycle/drug effects; Trophozoites/drug effects
Gene Expression Profiling of Maslinic Acid-treated MCF-7 Breast Cancer Cells Using Nanostring nCounter Pancancer Pathway Panel

Tan SY, Foo CN, Ng FL, Tan CH, Lim YM

Gene, 2025 Jan 30;935:149043.
PMID: 39486662 DOI: 10.1016/j.gene.2024.149043

Breast cancer remains a significant global health concern, impacting millions of women every year. Maslinic acid (MA), a pentacyclic triterpene has been found to exert promising anticancer effect in various cancers, including breast cancer, yet the underlying mechanisms remain unclear. This study aims to elucidate the anticancer properties of MA via gene expression profiles in breast cancer cells. Cytotoxicity assay results revealed that MCF-7 exerts the highest sensitivity after 72 h of MA treatment followed by T-47D and MDA-MB-231. MCF-7 were then selected for in-depth analysis using the Nanostring nCounter Pancancer Pathway Panel to analyze the differential expression of genes (DEGs). Across three time points (24, 48, and 72 h), 20 significant DEGs were identified, of which 5 were upregulated and 15 were downregulated. In silico analysis indicated that these DEGs were involved in Pathway of Cancer, Focal Adhesion-PI3K-mTOR Signaling Pathway, PI3K-Akt, and Ras Signaling Pathway. The regulation of these DEGs contributes to several cellular activities such as apoptosis, inhibition of cell proliferation, cell cycle and survival, reduction of glycolysis, angiogenesis, and DNA repair. Additionally, the unfolded protein response emerged as a noteworthy biological process in this study. This study unravels the molecular mechanisms underpinning the therapeutic potential of MA against breast cancer.

Matched MeSH terms: Apoptosis/drug effects; Cell Proliferation/drug effects
Fulltext Physiochemical and phytochemical properties of wax apple (Syzygium samarangense [Blume] Merrill & L. M. Perry var. Jambu Madu) as affected by growth regulator application

Moneruzzaman Khandaker M, Nasrulhaq Boyce A, Osman N, Sharif Hossain A

ScientificWorldJournal, 2012;2012:728613.
PMID: 22701370 DOI: 10.1100/2012/728613

This study represents the first paper of the effects of growth regulators on the physiochemical and phytochemical properties of the wax apple fruit, a widely cultivated fruit tree in southeast Asia. Net photosynthesis, sucrose phosphate synthase (SPS) activity, peel color, fruit firmness, juice content, pH value, total soluble solids (TSSs), and the sugar acid ratio were all significantly increased in growth regulators (PGRs) treated fruits. The application of gibberellin (GA(3)), naphthalene acetic acid (NAA), and 2,4-dichlorophenoxy acetic acid (2,4-D) significantly reduced titratable acidity and increased total sugar and carbohydrate content compared to the control. The 50 mg/L GA₃, 10 mg/L NAA, and 5 mg/L 2,4-D treatments produced the greatest increases in phenol and flavonoid content; vitamin C content was also higher for these treatments. PGR treatment significantly affected chlorophyll, anthocyanin, and carotene content and produced higher phenylalanine ammonia lyase (PAL) and antioxidant activity levels. There was a positive correlation between peel color and TSS and antioxidant activity and both phenol and flavonoid content and PAL activity and anthocyanin formation. A taste panel assessment was also performed, and the highest scores were given to fruits that had been treated with GA₃ or auxin. The study showed that application of 50 mg/L GA₃, 10 mg/L NAA, and 5 mg/L 2,4-D once a week from bud development to fruit maturation increased the physiochemical and phytochemical properties of wax apple fruits.

Matched MeSH terms: Fruit/drug effects*; Syzygium/drug effects*
Fulltext Cytotoxicity effect of degraded and undegraded kappa and iota carrageenan in human intestine and liver cell lines

Ariffin SH, Yeen WW, Abidin IZ, Abdul Wahab RM, Ariffin ZZ, Senafi S

BMC Complement Altern Med, 2014;14:508.
PMID: 25519220 DOI: 10.1186/1472-6882-14-508

Carrageenan is a linear sulphated polysaccharide extracted from red seaweed of the Rhodophyceae family. It has broad spectrum of applications in biomedical and biopharmaceutical field. In this study, we determined the cytotoxicity of degraded and undegraded carrageenan in human intestine (Caco-2; cancer and FHs 74 Int; normal) and liver (HepG2; cancer and Fa2N-4; normal) cell lines.

Matched MeSH terms: Cell Survival/drug effects; Intestines/drug effects*; Liver/drug effects*; Apoptosis/drug effects; Cell Proliferation/drug effects*
Expression profile of genes modulated by Aloe emodin in human U87 glioblastoma cells

Haris K, Ismail S, Idris Z, Abdullah JM, Yusoff AA

Asian Pac J Cancer Prev, 2014;15(11):4499-505.
PMID: 24969876

Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.

Matched MeSH terms: Down-Regulation/drug effects; Up-Regulation/drug effects; Apoptosis/drug effects; Cell Proliferation/drug effects; Transcriptome/drug effects*
Fulltext Effect of acacia honey on cultured rabbit corneal keratocytes

Ker-Woon C, Abd Ghafar N, Hui CK, Mohd Yusof YA

BMC Cell Biol., 2014;15:19.
PMID: 24885607 DOI: 10.1186/1471-2121-15-19

Acacia honey is a natural product which has proven to have therapeutic effects on skin wound healing, but its potential healing effects in corneal wound healing have not been studied. This study aimed to explore the effects of Acacia honey (AH) on corneal keratocytes morphology, proliferative capacity, cell cycle, gene and protein analyses. Keratocytes from the corneal stroma of six New Zealand white rabbits were isolated and cultured until passage 1. The optimal dose of AH in the basal medium (FD) and medium containing serum (FDS) for keratocytes proliferation was identified using MTT assay. The morphological changes, gene and protein expressions of aldehyde dehydrogenase (ALDH), marker for quiescent keratocytes and vimentin, marker for fibroblasts were detected using q-RTPCR and immunocytochemistry respectively. Flowcytometry was performed to evaluate the cell cycle analysis of corneal keratocytes.

Matched MeSH terms: Cell Cycle/drug effects; Cell Survival/drug effects; Gene Expression Regulation/drug effects; Cell Proliferation/drug effects; Corneal Keratocytes/drug effects*
Fulltext Diverse effects of lead nitrate on the proliferation, differentiation, and gene expression of stem cells isolated from a dental origin

Abdullah M, Rahman FA, Gnanasegaran N, Govindasamy V, Abu Kasim NH, Musa S

ScientificWorldJournal, 2014;2014:235941.
PMID: 24616615 DOI: 10.1155/2014/235941

Lead (Pb(2+)) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb(2+) toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb(2+) concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb(2+) on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb(2+) treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb(2+) continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb(2+) exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

Matched MeSH terms: Cell Differentiation/drug effects*; Dental Pulp/drug effects*; Stem Cells/drug effects*; Gene Expression/drug effects*; Cell Proliferation/drug effects*

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