Displaying publications 61 - 80 of 289 in total

Abstract:
Sort:
  1. Nordin N, Fadaeinasab M, Mohan S, Mohd Hashim N, Othman R, Karimian H, et al.
    PLoS One, 2016;11(5):e0154023.
    PMID: 27136097 DOI: 10.1371/journal.pone.0154023
    Drug resistance presents a challenge in chemotherapy and has attracted research interest worldwide and particular attention has been given to natural compounds to overcome this difficulty. Pulchrin A, a new compound isolated from natural products has demonstrated novel potential for development as a drug. The identification of pulchrin A was conducted using several spectroscopic techniques such as nuclear magnetic resonance, liquid chromatography mass spectrometer, infrared and ultraviolet spectrometry. The cytotoxicity effects on CAOV-3 cells indicates that pulchrin A is more active than cisplatin, which has an IC50 of 22.3 μM. Significant changes in cell morphology were present, such as cell membrane blebbing and formation of apoptotic bodies. The involvement of phosphatidylserine (PS) in apoptosis was confirmed by Annexin V-FITC after a 24 h treatment. Apoptosis was activated through the intrinsic pathway by activation of procaspases 3 and 9 as well as cleaved caspases 3 and 9 and ended at the executioner pathway, with the occurrence of DNA laddering. Apoptosis was further confirmed via gene and protein expression levels, in which Bcl-2 protein was down-regulated and Bax protein was up-regulated. Furthermore, the CAOV-3 cell cycle was disrupted at the G0/G1 phase, leading to apoptosis. Molecular modeling of Bcl-2 proteins demonstrated a high- binding affinity, which inhibited the function of Bcl-2 proteins and led to cell death. Results of the current study can shed light on the development of new therapeutic agents, particularly, human ovarian cancer treatments.
    Matched MeSH terms: Biological Products/pharmacology*; Biological Products/chemistry*
  2. Siti Balkis Budin, Hawa Ismail, Pek LC
    Sains Malaysiana, 2013;42:707-713.
    Abundant natural products with medicinal properties have been used as food and traditional medicine for diabetes mellitus all over the world. Psidium guajava fruit from the family of Myrtaceae has gained attention for its antioxidant potential. This study was conducted to determine the effects of P. guajava fruit peel aqueous extract on oxidative stress of pancreas in streptozotocin-induced (45 mg/kg) diabetic rats. Diabetic rats were administered with 400 mg/kg of aqueous extract of P. guajava fruit peel daily for 28 days duration. The results showed that diabetic rats supplemented with P. guajava extract did not cause significant difference in blood glucose level (p>0.05) as compared with diabetic rats alone. For oxidative stress evaluation, malondialdehyde (MDA) and protein carbonyl level were significantly lower and the activity of superoxide dismutase (SOD) and glutathione (GSH) level were significantly higher (p<0.05) in P. guajava supplemented rats compared with non-supplemented diabetic rats. However, histological observation showed that supplementation of P. guajava extract did not give protective effects towards alterations in pancreas histology in diabetic rats. The findings suggested that aqueous extract of P. guajava fruit peel supplementation has the ability to reduce oxidative stress in pancreas of diabetic rats and may play a role in reducing the development of diabetic complications.
    Matched MeSH terms: Biological Products
  3. Agyei D, Ahmed I, Akram Z, Iqbal HM, Danquah MK
    Protein Pept Lett, 2017;24(2):94-101.
    PMID: 28017145 DOI: 10.2174/0929866523666161222150444
    Bioactive proteins and peptides are recognised as novel therapeutic molecules with varying biological properties for potential medical applications. Development of protein and peptidebased therapeutic products for human use is growing steadily as they continue to receive an increasing rate of approval by the United States Food and Drugs Administration (US FDA). In this short review, we describe the current status and methodologies involved in the synthesis of protein and peptide biopharmaceuticals with an emphasis on the drivers and restrains to their exploitation in the therapeutic products sector.
    Matched MeSH terms: Biological Products/chemical synthesis; Biological Products/metabolism; Biological Products/pharmacology
  4. Ridzuan NRA, Rashid NA, Othman F, Budin SB, Hussan F, Teoh SL
    Mini Rev Med Chem, 2019;19(14):1134-1143.
    PMID: 30894108 DOI: 10.2174/1389557519666190320124438
    Cisplatin is a widely used antineoplastic agent for the treatment of metastatic tumors, advanced bladder cancer and many other solid tumors. However, at higher doses, toxicities such as nephrotoxicity may appear. Cisplatin leads to DNA damage and subsequently renal cell death. Besides that, oxidative stress is also implicated as one of the main causes of nephrotoxicity. Several studies showed that numerous natural products: ginseng, curcumin, licorice, honey and pomegranate were able to reduce the oxidative stress by restoring the levels of antioxidant enzymes and also at the same time act as an anti-inflammatory agent. Furthermore, pre-treatment with vitamin supplementation, such as vitamin C, E and riboflavin markedly decreased serum urea and increased the levels of antioxidant enzymes in the kidney even after cisplatin induction in cancer patients. These natural products possess potent antioxidant and anti-inflammatory medicinal properties, and they can be safely used as a supplementary regime or combination therapy against cisplatin-induced nephrotoxicity. The present review focused on the protective role of a few natural products which is widely used in folk medicines in cisplatin-induced nephrotoxicity.
    Matched MeSH terms: Biological Products
  5. Lum PT, Sekar M, Gan SH, Bonam SR, Shaikh MF
    ACS Chem Neurosci, 2021 Feb 03;12(3):391-418.
    PMID: 33475334 DOI: 10.1021/acschemneuro.0c00824
    Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.
    Matched MeSH terms: Biological Products
  6. Nur Izzati Mansor, Nuratiqah Azmi, Ling, King-Hwa, Rozita Rosli, Zurina Hassan, Norshariza Nordin
    Neuroscience Research Notes, 2019;2(1):16-30.
    MyJurnal
    The use of in vitromodel for screening pharmacological compounds or natural products has gained global interest. The choice of cells to be manipulated plays a vital role in coming up with the best-suitedmodel for specific diseases, including neurodegenerativediseases (ND). A good in vitro ND model should provide appropriate morphological and molecular features that mimic ND conditions where it can be used to screen potential properties of natural products in addition to unravelling the molecular mechanisms of ND. In this mini review, we intend to demonstrate two prospective stem cell lines as the potential cell source for in vitroND model and compare them to the commonly used cells. The common source of cells that have been usedas the in vitroND models is discussedbefore going into details talking about the two prospective stem cell lines.
    Matched MeSH terms: Biological Products
  7. Ghosh S, Al-Sharify ZT, Maleka MF, Onyeaka H, Maleke M, Maolloum A, et al.
    Environ Sci Pollut Res Int, 2022 Aug;29(39):58628-58647.
    PMID: 35794320 DOI: 10.1007/s11356-022-21652-6
    This current study review provides a brief review of a natural bee product known as propolis and its relevance toward combating SARS-CoV viruses. Propolis has been utilized in medicinal products for centuries due to its excellent biological properties. These include anti-oxidant, immunomodulatory, anti-inflammatory, anti-viral, anti-fungal, and bactericidal activities. Furthermore, studies on molecular simulations show that flavonoids in propolis may reduce viral replication. While further research is needed to validate this theory, it has been observed that COVID-19 patients receiving propolis show earlier viral clearance, enhanced symptom recovery, quicker discharge from hospitals, and a reduced mortality rate relative to other patients. As a result, it appears that propolis could probably be useful in the treatment of SARS-CoV-2-infected patients. Therefore, this review sought to explore the natural properties of propolis and further evaluated past studies that investigated propolis as an alternative product for the treatment of COVID-19 symptoms. In addition, the review also highlights the possible mode of propolis action as well as molecular simulations of propolis compounds that may interact with the SARS-CoV-2 virus. The activity of propolis compounds in decreasing the impact of COVID-19-related comorbidities, the possible roles of such compounds as COVID-19 vaccine adjuvants, and the use of nutraceuticals in COVID-19 treatment, instead of pharmaceuticals, has also been discussed.
    Matched MeSH terms: Biological Products*
  8. Noor Hafizah, Y, Maskat, M. Y., Wan Aida, W. M., Maaruf, A. G.
    MyJurnal
    Storage study of mengkudu (Morinda citrifolia L.) extract was carried out to determine the effects
    of canning and storage period on pH, total polyphenol content, antioxidant activity, intensity of off-odour and aroma acceptance. Uncanned (control) and canned extract were stored for 0, 8, 16 and 24 weeks under room temperature. Results showed canning resulted in a significant (p
    Matched MeSH terms: Biological Products
  9. Mohd Zaid NA, Sekar M, Bonam SR, Gan SH, Lum PT, Begum MY, et al.
    Drug Des Devel Ther, 2022;16:23-66.
    PMID: 35027818 DOI: 10.2147/DDDT.S326332
    The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, well-tolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.
    Matched MeSH terms: Biological Products/therapeutic use*
  10. Samat N, Tan PJ, Shaari K, Abas F, Lee HB
    Anal Chem, 2014 Feb 4;86(3):1324-31.
    PMID: 24405504 DOI: 10.1021/ac403709a
    Photodynamic therapy (PDT) is an alternative treatment for cancer that involves administration of a photosensitive drug or photosensitizer that localizes at the tumor tissue followed by in situ excitation at an appropriate wavelength of light. Tumour tissues are then killed by cytotoxic reactive oxygen species generated by the photosensitizer. Targeted excitation and photokilling of affected tissues is achieved through focal light irradiation, thereby minimizing systemic side effects to the normal healthy tissues. Currently, there are only a small number of photosensitizers that are in the clinic and many of these share the same structural core based on cyclic tetrapyrroles. This paper describes how metabolic tools are utilized to prioritize natural extracts to search for structurally new photosensitizers from Malaysian biodiversity. As proof of concept, we analyzed 278 photocytotoxic extracts using a hyphenated technique of liquid chromatography-mass spectrometry coupled with principal component analysis (LC-MS-PCA) and prioritized 27 extracts that potentially contained new photosensitizers for chemical dereplication using an in-house UPLC-PDA-MS-Photocytotoxic assay platform. This led to the identification of 2 new photosensitizers with cyclic tetrapyrrolic structures, thereby demonstrating the feasibility of the metabolic approach.
    Matched MeSH terms: Biological Products/analysis*; Biological Products/isolation & purification; Biological Products/therapeutic use
  11. Shrestha S, Poudel RS, Kc B, Poudel BK, Sapkota B, Sharma S, et al.
    PMID: 32266073 DOI: 10.1186/s40545-020-0203-0
    Objective: To assess the variation in price among different brands of anticancer medicines available in hospital pharmacies at Nepalese cancer hospitals.

    Methods: The price of different brands of the same anticancer medicines available in the hospital pharmacies of two cancer hospitals was assessed. Prices of different dosage forms such as a single tablet, capsule and vial were calculated. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical industries was determined, and the percentage variation in price was calculated. The prices of medicines (brands) were also compared with the price determined by the government where available.

    Results: Price variation was assessed for 31 anticancer medicines belonging to six broad categories. Prices were found to vary maximally among the following medicines, each belonging to separate categories: among alkylating agents, the price of temozolomide 100 mg capsule varied 308%; among antimetabolite agents, the price of pemetrexed 500 mg injection varied 134%; among hormonal drugs, the price of letrozole 2.5 mg tablet varied 200%; among antibody class, the price of trastuzumab 440 mg injection varied 73%; among natural products, the price of irinotecan 100 mg injection varied 590%; and among miscellaneous agents, the price of bortezomib 2 mg injection varied 241%. There was a significant difference in the mean MRP of the alkylating agents with the antimetabolites (p-value 0.006) and the monoclonal antibody (p-value

    Matched MeSH terms: Biological Products
  12. Tang DYY, Khoo KS, Chew KW, Tao Y, Ho SH, Show PL
    Bioresour Technol, 2020 May;304:122997.
    PMID: 32094007 DOI: 10.1016/j.biortech.2020.122997
    Microalgae are autotroph organisms that utilise light energy to synthesize various high-value bioactive compounds such as polysaccharides, proteins and lipids. Due to its fast growth rate and capability to survive in harsh environment, microalgae nowadays are applied in various industrial areas. The process of obtaining microalgae-based biomolecules starts with the selection of suitable microalgae strain, cultivation, followed by downstream processing of the biomass (i.e., pre-treatment, harvesting, extraction and purification). The end products of the processes are biofuels and other valuable bioproducts. Nevertheless, low production yield and high-cost downstream processes are the emerging bottlenecks which need to be addressed in the upscaling of extracted compounds from microalgae biomass. To conclude, tremendous efforts are required to overcome these challenges to revolutionize microalgae into a novel and green factory of different bioactive compounds for industrial necessities to satisfy and fulfil global demands.
    Matched MeSH terms: Biological Products*
  13. Mourya A, Shubhra, Bajwa N, Baldi A, Singh KK, Pandey M, et al.
    Mini Rev Med Chem, 2023;23(9):992-1032.
    PMID: 35546778 DOI: 10.2174/1389557522666220511140527
    Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodeling and inflammaging. To counteract the inflammation, synovium releases various inflammatory and immune mediators along with metabolic intermediates, which further worsens the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs, opioids, SNRIs, etc., providing symptomatic treatment and functional improvement instead of suppressing OA progression. Long-term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional medicine and are promising alternatives to conventional drugs with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases is elusive and uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggest that the presence of carbonyl group in the 2nd position, chloro in the 6th and an electron- withdrawing group at the 7th position exhibit enhanced COX-2 inhibition activity in OA. On the other hand, the presence of a double bond at the C2-C3 position of C ring in flavonoids plays an important role in Nrf2 activation. Moreover, with the advancements in the understanding of OA progression, SARs (structure-activity relationships) of phytochemicals and integration with nanotechnology have provided great opportunities for developing phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical-based drug therapy.
    Matched MeSH terms: Biological Products/pharmacology; Biological Products/therapeutic use
  14. Kong YR, Tay KC, Su YX, Wong CK, Tan WN, Khaw KY
    Molecules, 2021 Jan 30;26(3).
    PMID: 33573300 DOI: 10.3390/molecules26030728
    Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.
    Matched MeSH terms: Biological Products/therapeutic use; Biological Products/chemistry
  15. Nagarajan K, Tong WY, Leong CR, Tan WN
    J Microbiol Biotechnol, 2021 Apr 28;31(4):493-500.
    PMID: 32627761 DOI: 10.4014/jmb.2005.05012
    Endophytic fungi are symbiotically related to plants and spend most of their life cycle within them. In nature, they have a crucial role in plant micro-ecosystem. They are harnessed for their bioactive compounds to counter human health problems and diseases. Endophytic Diaporthe sp. is a widely distributed fungal genus that has garnered much interest within the scientific community. A substantial number of secondary metabolites have been detected from Diaporthe sp. inhabited in various plants. As such, this minireview highlights the potential of Diaporthe sp. as a rich source of bioactive compounds by emphasizing on their diverse chemical entities and potent biological properties. The bioactive compounds produced are of significant importance to act as new lead compounds for drug discovery and development.
    Matched MeSH terms: Biological Products/chemistry*
  16. Ramasamy C
    Infect Disord Drug Targets, 2015;15(3):141-52.
    PMID: 26321324
    OBJECTIVES: Polyphenols constitute the major component in green tea, which represent a cluster known as catechins. The presence of polyphenols, especially the amino acid theanine and catechins with its antioxidant properties in green tea make them ideal for medicinal- dental applications. The objective of the paper is to delineate the role of green tea polyphenols in periodontal disease.

    METHODS: The Pub med data base was searched for human clinical studies, reviews pertinent to application of green tea polyphenols in periodontal health dating from Sep 1980- Sep 2014.

    RESULTS: The retrieved inference from the epidemiological surveys, in vitro studies and overviews of polyphenols, postulate green tea as potential natural antioxidant. Green tea mouthwashes possess limitations, which make them ineffective during the chronic stages of periodontitis. Human studies reveal that the prognosis of periodontal disease is better when the green tea catechins are used via local drug delivery.

    CONCLUSION: The maintenance of periodontal health could be enhanced by emphasizing the habit of drinking green tea in periodontitis patients. The future scope of the research demands the analysis of polyphenols at molecular level to have a better understanding of its overwhelming applications.

    Matched MeSH terms: Biological Products
  17. Hassanain Al-Talib, Nur Izzati Syamimi Mohd Nasir, Hafizuddin Yaziz, Nur Fatihah Zulkafli, Nur Aqidah Adani, Ahmad Ikhwan Noor Rashidi, et al.
    Axillary malodor is caused by microbial biotransformation of non-smelling molecules present in apocrine secretions, into volatile odorous molecules. This study aimed to determine the antimicrobial activities of potassium aluminium salts (alum) against four malodor-producing axillary bacterial flora, as an alternative natural product for reducing axillary malodor.
    Matched MeSH terms: Biological Products
  18. Phan CW, Wong WL, David P, Naidu M, Sabaratnam V
    PMID: 22812497 DOI: 10.1186/1472-6882-12-102
    Drugs dedicated to alleviate neurodegenerative diseases like Parkinson's and Alzheimer's have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal.
    Matched MeSH terms: Biological Products/pharmacology*; Biological Products/therapeutic use; Biological Products/chemistry
  19. Jantan I, Ahmad W, Bukhari SN
    Front Plant Sci, 2015;6:655.
    PMID: 26379683 DOI: 10.3389/fpls.2015.00655
    The phagocyte-microbe interactions in the immune system is a defense mechanism but when excessively or inappropriately deployed can harm host tissues and participate in the development of different non-immune and immune chronic inflammatory diseases such as autoimmune problems, allergies, some rheumatoid disorders, cancers and others. Immunodrugs include organic synthetics, biological agents such as cytokines and antibodies acting on single targets or pathways have been used to treat immune-related diseases but with limited success. Most of immunostimulants and immunosuppressants in clinical use are the cytotoxic drugs which possess serious side effects. There is a growing interest to use herbal medicines as multi-component agents to modulate the complex immune system in the prevention of infections rather than treating the immune-related diseases. Many therapeutic effects of plant extracts have been suggested to be due to their wide array of immunomodulatory effects and influence on the immune system of the human body. Phytochemicals such as flavonoids, polysaccharides, lactones, alkaloids, diterpenoids and glycosides, present in several plants, have been reported to be responsible for the plants immunomodulating properties. Thus the search for natural products of plant origin as new leads for development of potent and safe immunosuppressant and immunostimulant agents is gaining much major research interest. The present review will give an overview of widely investigated plant-derived compounds (curcumin, resveratrol, epigallocatechol-3-gallate, quercetin, colchicine, capsaicin, andrographolide, and genistein) which have exhibited potent effects on cellular and humoral immune functions in pre-clinical investigations and will highlight their clinical potential.
    Matched MeSH terms: Biological Products
  20. Rasool S, Mohamed R
    Protoplasma, 2016 Sep;253(5):1197-209.
    PMID: 26364028 DOI: 10.1007/s00709-015-0884-4
    Cytochrome P450s constitute the largest family of enzymatic proteins in plants acting on various endogenous and xenobiotic molecules. They are monooxygenases that insert one oxygen atom into inert hydrophobic molecules to make them more reactive and hydro-soluble. Besides for physiological functions, the extremely versatile cytochrome P450 biocatalysts are highly demanded in the fields of biotechnology, medicine, and phytoremediation. The nature of reactions catalyzed by P450s is irreversible, which makes these enzymes attractions in the evolution of plant metabolic pathways. P450s are prime targets in metabolic engineering approaches for improving plant defense against insects and pathogens and for production of secondary metabolites such as the anti-neoplastic drugs taxol or indole alkaloids. The emerging examples of P450 involvement in natural product synthesis in traditional medicinal plant species are becoming increasingly interesting, as they provide new alternatives to modern medicines. In view of the divergent roles of P450s, we review their classification and nomenclature, functions and evolution, role in biosynthesis of secondary metabolites, and use as tools in pharmacology.
    Matched MeSH terms: Biological Products
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links