Displaying publications 61 - 80 of 81 in total

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  1. Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019 Feb 14.
    PMID: 30767742 DOI: 10.2174/1389450120666190214141626
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess cerebrospinal fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, blurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of cerebrospinal fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

  2. Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019;20(10):1041-1057.
    PMID: 30767741 DOI: 10.2174/1389450120666190214121342
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess Cerebrospinal Fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, slurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

  3. Arunachalam M, Ramesh M, Thiagarajan V, Singla SK, Mudhol S, Muthukumar SP
    Curr Drug Targets, 2021;22(14):1688-1703.
    PMID: 33618645 DOI: 10.2174/1389450122666210222163528
    The neuron is high-energy utilizing tissue. The rate of neuronal cell respiration is higher than in other cells. Cellular respiration occurs with mitochondria. The healthy production and functions of mitochondria play a key role in the maintenance of healthy neurons. In pathological conditions such as neurodegenerative diseases, healthy mitochondria help to alleviate pathological events in neuronal cells. Conversely, mitochondrial dysfunction promotes the acceleration of the neurodegenerative process. Furthermore, glial-derived mitochondria contribute to multiple roles in the regulation of healthy neuron functions. It also supports releasing of the neurotransmitters; generation of the impulses, regulation of the membrane potential and molecular dynamics; controlling of the axonal transport; controlling of the mitochondrial fission and fusion functions in the peripheral as well as the central nervous system. Moreover, it plays a key role in the regeneration process of neuronal cells. Therefore, healthy mitochondria can provide a healthy environment for neuronal cell function and can treat neurodegenerative disorders. In this review, we explore the current view of healthy mitochondria and their role in healthy neuronal functions.
  4. Chung PY
    Curr Drug Targets, 2018;19(7):832-840.
    PMID: 28891454 DOI: 10.2174/1389450118666170911114604
    BACKGROUND: Bacterial resistance to antibiotics is one of the most serious challenge to global public health. The introduction of new antibiotics in clinical settings, i.e. agents that belong to a new class of antibacterials, act on new targets or has a novel mechanisms of action, may not be sufficient to cope with the emergence of multidrug-resistant pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Escherichia coli, which are increasingly prevalent in healthcare settings in Europe, the USA and Asia. Hence, coordinated efforts in minimizing the risk of spread of resistant bacteria and renewing research efforts in the search for novel antibacterial agents are urgently needed to manage this global crisis.

    OBJECTIVE: This review highlights the challenges and potential in using current technologies in the discovery and development of novel antibacterial agents to keep up with the constantly evolving resistance in bacteria.

    CONCLUSION: With the explosion of bacterial genomic data and rapid development of new sequencing technologies, the understanding of bacterial pathogenesis and identification of novel antibiotic targets have significantly improved.

  5. Mohamad NV, Ima-Nirwana S, Chin KY
    Curr Drug Targets, 2018;19(8):898-906.
    PMID: 28914204 DOI: 10.2174/1389450118666170913162739
    Cognitive function and testosterone level of men decline concurrently with age. Low testosterone levels are associated with higher risk of Alzheimer's disease and mild cognitive impairment in men. There are continuous debates on whether this relationship is casual. This paper aims to summarize the current evidence on the association between testosterone level and cognitive function in elderly men. The presence of testosterone, androgen receptor and its responsive genes indicates that testosterone has biological functions in the central nervous system. The ability of the body to convert testosterone into estrogen suggests that part of the actions of testosterone could be mediated by estrogen. Observational studies generally showed that low endogenous testosterone levels were associated with poor cognitive performance in healthy elderly men. Testosterone substitution exerted positive effects on certain cognitive domains in normal and hypogonadal elderly men. In conclusion, testosterone may influence cognitive function in elderly men and its substitution may be considered in men with cognitive impairment and testosterone deficiency.
  6. Tumpang MA, Ramli NA, Hussain Z
    Curr Drug Targets, 2018;19(6):674-700.
    PMID: 28914203 DOI: 10.2174/1389450118666170913162147
    BACKGROUND: Phytomedicines have been well-accepted alternative complementary therapies for the treatment of a wide range of acute and chronic skin inflammatory diseases including chronic herpes, prurigo, psoriasis, and atopic dermatitis (AD). A plethora of in vitro and in vivo studies have evidenced the therapeutic viability of phytomedicines, polyherbal formulations, plant-based materials and their decoctions for the treatment of mild-to-severe AD.

    OBJECTIVE: This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of phytomedicines for the treatment of AD and explore their anti-AD efficacy.

    RESULTS: The critical analysis of a wide algorithm of herbal medicines revealed that their remarkable anti-AD efficacy is attributed to their potential of reducing erythema intensity, oedema, inflammation, transepidermal water loss (TEWL) and a remarkable suppression of mRNA expression of ADassociated inflammatory biomarkers including histamine, immunoglobulin (Ig)-E, prostaglandins, mast cells infiltration and production of cytokines and chemokines in the serum and skin biopsies.

    CONCLUSION: In conclusion, herbal medicines hold great promise as complementary and alternative therapies for the treatment of mild-to-moderate AD when used as monotherapy and for the treatment of moderate-to-severe AD when used in conjunction with other pharmacological agents.

  7. Wong SK, Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2018;19(8):888-897.
    PMID: 28914205 DOI: 10.2174/1389450118666170913161030
    Depression is a common psychiatric disorder that decreases the quality of life and increases the mortality of patients. It incurs significant healthcare costs if left untreated. Even though intervention with antidepressants can reduce depressive symptoms, side effects are often an issue and relapse is very common. Vitamin D, commonly known as the sunshine vitamin, is an essential fat-soluble vitamin for the absorption of calcium to prevent rickets (children) and osteomalacia (adults). Evidence on a possible relationship between vitamin D deficiency and depression is growing. In this review, the authors summarized the evidence on the association between vitamin D status and depression in human observational studies, followed by clinical trials to evaluate the effects of vitamin D supplementation in treating depression. In conclusion, vitamin D deficiency may be associated with an increased risk or severity of depression. Supplementation of vitamin D may confer protection for depressed patients.
  8. Theng YM, Wahab S, Wahab NAA, Sidi H, Das S
    Curr Drug Targets, 2019;20(2):173-181.
    PMID: 29046149 DOI: 10.2174/1389450118666171017163741
    Nicotine dependence has progressively become a foremost community health interest in both the developed and developing nations due to the economic burden and health-related problems. Smoking was significantly higher among patients with schizophrenia in comparison to the general population. Nicotine dependence is not only associated with public stress, but among patients with schizophrenia, smoking brings major challenges to the management. Nicotine may diminish the therapeutic efficacy of the bioavailability of the psychopharmacological agents in-vivo. These duo perturbations, i.e. two clinical conditions co-existed may prevent psychotic symptoms remission among patients suffering from schizophrenia who smoke at the same time. The aim of this review was to highlight the role of pharmacological treatment options and strategies for patients with nicotine dependence in schizophrenia with emphasis on the underlying neurobiological process. The role of nicotine replacement therapy, i.e. norepinephrine-dopamine reuptake inhibition (NDRI) e.g. bupropion and selective partial agonist of α4β2 and full α7-nicotinic acetylcholine receptor e.g. varenicline was deliberated. An ideal choice of drug targets for patients with schizophrenia with nicotine dependence is pivotal to foster a better therapeutic alliance.
  9. Mai CW, Chung FF, Leong CO
    Curr Drug Targets, 2017;18(11):1259-1268.
    PMID: 27993111 DOI: 10.2174/1389450117666161216125344
    BACKGROUND: Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target.

    CONCLUSION: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.

  10. 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.

  11. Thent ZC, Zaidun NH, Azmi MF, Senin MI, Haslan H, Salehuddin R
    Curr Drug Targets, 2017;18(6):734-750.
    PMID: 27919208 DOI: 10.2174/1389450118666161205125548
    Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus. In CRC-independent of diabetes mellitus, highly deregulation of PI3K/AKT pathway is found which activates the downstream mammalian target of rapamycin (mTOR). Metformin inhibits cancer growth in colon by suppressing the colonic epithelial proliferation by inhibiting the mTOR pathway. Metformin exerts its anti-neoplastic effects by acting on tumour suppressor pathway via activating the adenosine monophosphate.activated protein kinase (AMPK) signaling pathway. Metformin interrupts the glucose metabolism by activating the AMPK. Metformin reduces tumour cell growth and metastasis by activating the p53 tumour suppressor gene. In addition to its therapeutic benefits, metformin is easily accessible, cost effective with better tolerance to the patients compared to the chemotherapeutic agents. This review summarised modern findings on the therapeutic applications of metformin on the colorectal cancer with no evidences of diabetes mellitus.
  12. Chin KY, Mark-Lee WF
    Curr Drug Targets, 2018;19(12):1359-1365.
    PMID: 28950813 DOI: 10.2174/1389450118666170925154025
    Mitragyna speciosa is a tropical plant with narcotic effects. The antinociceptive effects of its crude extracts, bioactive compounds and structurally modified derivatives have been examined in rodent models. This review aims to summarize the evidence on the antinociceptive effects of M. speciosa and its derivatives and explore whether they can offer an alternative to morphine in pain management. Methanolic and alkaloid extracts of M. speciosa were shown to attenuate the nociceptive response in rodents. Mitragynine and 7-hydroxymitragynine offered better antinociceptive effects than crude extracts. Structurally modified derivatives of 7-hydroxymitragynine, such as MGM-9, MGM- 15, MGM-16, demonstrated superior antinociceptive effects compared to morphine. M. speciosa and its derivatives mainly act on the opioid receptor, but receptor subtypes specificity differs between each compound. The tolerance and adverse side effects of M. speciosa and its derivatives are similar with morphine. The affinity of MGM-9 on kappa-opioid receptor could potentially limit the effects of drug dependence. In conclusion, M speciosa derivatives can offer alternatives to morphine in controlling chronic pain. Structural modification of mitragynine and 7-hydroxymitragynine can generate compounds with higher potency and lesser side-effects. Human clinical trials are required to validate the use of these compounds in clinical setting.
  13. Mohamed N, Muhammad N, Shuid AN, Soelaiman IN
    Curr Drug Targets, 2018;19(12):1424-1430.
    PMID: 28950810 DOI: 10.2174/1389450118666170925154428
    Nicotine is one of the most abused substances worldwide and can cause several harmful effects on health. One of the harmful effects, which is often ignored, is osteoporosis. Smoking has been shown to cause a decrease in bone mineral density in humans. Animal studies have proven that nicotine exerts negative effects on bone. The number of people who smoke increases each day. Those who smoke start at a very young age and they usually smoke for years. This will increase the risk of developing osteoporosis. As the prevalence of osteoporosis increases, the risk of fractures also increases. The major concerns are disability following fractures, mortality due to complications after fractures and the increasing cost of management and therapy. This paper will review the effects of nicotine on bone and the potential natural products which can be used as treatment for nicotine-induced osteoporosis.
  14. Yee A, Ng CG, Seng LH
    Curr Drug Targets, 2018;19(12):1412-1423.
    PMID: 29149828 DOI: 10.2174/1389450118666171117131151
    BACKGROUND: Vortioxetine is a multimodal antidepressant that has been developed for the treatment of major depressive and anxiety disorders. The aim of this review is to quantitatively synthesize all data of the efficacy, safety and tolerability of Vortioxetine in treating anxiety disorder.

    METHOD: Terms of "Vortioxetine" OR "LuAA21004" AND "anxiety" OR "fear" OR "panic" OR "phobia" were searched. A total of two phase II and five phase III clinical trials were found.

    RESULTS: Vortioxetine was overall superior to placebo in terms of the mean change from baseline in HAM-A total score at week 8 with the pool effect size of -2.95, 95% CIs, -4.37 to -1.53, p<0.01. The patients who received 5 mg of Vortioxetine had higher response rate when compared to placebo (pooled odds ratio=1.4, 95% CI = 1.08 to 1.82, p=0.01). However, the pooled odds ratio of the HAMA remission rate was not statistically significant for both Vortioxetine and placebo (pooled odds ratio= 1.06, 95% CI = 0.86 to 1.30, p=0.62). Although the discontinuation due to adverse effects was higher in Vortioxetine than placebo group (pooled OR= 1.55, 95% CI = 1.04 to 2.31, P= 0.037), the lack of efficacy (pooled OR= 0.39, 95% CI = 0.27 to 0.57, P<0.01) was higher in placebo than Vortioxetine group. Most of the adverse effects were mild and moderate. Overall, Vortioxetine displayed a good safety and tolerability profile.

    CONCLUSION: This review supports the use of Vortioxetine for anxiety disorder. However, further longterm placebo-control observational study or a post market survey would help in strengthening the evidence for this treatment modality.

  15. Azlina MFN, Qodriyah MS, Kamisah Y
    Curr Drug Targets, 2018;19(12):1456-1462.
    PMID: 29173163 DOI: 10.2174/1389450118666171122130338
    BACKGROUND: Scientific reports had shown that stress is related to numerous pathological changes in the body. These pathological changes can bring about numerous diseases and can significantly cause negative effects in an individual. These include gastric ulcer, liver pathology and neurobehavioral changes. A common pathogenesis in many diseases related to stress involves oxidative damage. Therefore, the administration of antioxidants such as vitamin E is a reasonable therapeutic approach. However, there is conflicting evidence about antioxidant supplementation.

    OBJECTIVE: The aim of this work was to summarize documented reports on the effects of tocopherol and tocotrienol on various pathological changes induced by stress.

    RESULTS AND CONCLUSION: This review will reveal the scientific evidence of enteral supplementation of vitamin E in the forms of tocotrienol and tocopherol in animal models of stress. These models mimic the stress endured by critically ill patients in a clinical setting and psychological stress in individuals. Positive outcomes from enteral feeding of vitamin E in reducing the occurrence of stress-induced pathological changes are discussed in this review. These positive findings include their ability to reduced stress-induced gastric ulcers, elevated liver enzymes and improved locomotors activity. Evidences showing tocotrienol and tocopherol effects are not just related to its ability to reduce oxidative stress but also acting on other mechanism, are discussed.

  16. Thu HE, Hussain Z, Mohamed IN, Shuid AN
    Curr Drug Targets, 2018;19(14):1657-1671.
    PMID: 29468964 DOI: 10.2174/1389450119666180219123815
    BACKGROUND: Eurycoma longifolia (E. longifolia) has gained widespread recognition due to its versatile pharmacological activities including aphrodisiac, anticancer, antimicrobial, antioxidant, anti-inflammatory, anxiolytic, anti-diabetic, ergogenic, insecticidal, anti-rheumatism, bone protection, and anti-ulcer effects.

    OBJECTIVE: This review was aimed to critically overview the literature and summarizes the antibacterial, antiprotozoal, and antifungal trends of E. longifolia and its medicinally active components.

    RESULTS: Besides its well-documented safety, efficacy, and tolerability, a plethora of in vitro, in vivo, and human clinical studies has evidenced the antimicrobial efficacy of E. longifolia and its bioactive constituents. Phytochemical screening of various types of extracts (methanolic, ethyl acetate, and nbutanolic) from different parts (roots, stem, and leaves) of E. longifolia displayed a dose-dependent antibacterial, antiprotozoal, and antifungal responses. Comparative analysis revealed that the root extract of E. longifolia exhibited the highest antimicrobial efficacy compared to other parts of the plant. Bioactivity-guided fractionation identified that among all of the medicinal compounds isolated/ extracted from different parts of E. longifolia, eurycomanone displayed the strongest antibacterial, antiprotozoal and antifungal activities.

    CONCLUSION: Based on the critical analysis of the literature, we identified that E. longifolia exhibits promising antibacterial, antiprotozoal, and antifungal efficacies against various pathogenic microbes and thus can be considered as a potential complementary and alternative antimicrobial therapy.

  17. Zaini S, Guan NC, Sulaiman AH, Zainal NZ, Huri HZ, Shamsudin SH
    Curr Drug Targets, 2018;19(12):1431-1455.
    PMID: 29484993 DOI: 10.2174/1389450119666180226125026
    Cancer patients are commonly associated with various physical and psychological symptoms. In palliative setting, the aims are to relieve those symptoms, improve quality of life, and increase medication adherence among cancer patients. Antidepressants are generally accepted for the treatment of depression among patients with or without cancer. Some other potential benefits of the antidepressants have been reported in cancer patients.

    OBJECTIVE: This study aims to review the use of antidepressants for physical and psychological symptoms in cancer patients.

    RESULTS: Our findings showed the mixed result of positive and negative findings in various symptoms associated with cancer patients. These studies are categorised according to the hierarchy of evidence from high to low level, namely randomised controlled trials, cohort studies, case-control studies, case series, case reports, as well as other type of publications. The majority of antidepressants used in cancer patients seem to be beneficial for the treatment of depression, anxiety, hot flashes and other symptoms such as sexual dysfunction, fatigue, nicotine dependence, vasomotor symptoms, executive functions, sleep problems, pruritus, as well as for hypochondriasis. While fluoxetine was found to be associated with the reduction of antiemetic property in ondansetron, mirtazapine was identified to be a good alternative in treating nausea and cachexia among cancer patients.

    CONCLUSION: More research studies with adequate statistical power are warranted to validate the use of antidepressants among cancer patients in treating these physical and psychological symptoms.

  18. Radzi NFM, Ismail NAS, Alias E
    Curr Drug Targets, 2018;19(9):1095-1107.
    PMID: 29412105 DOI: 10.2174/1389450119666180207092539
    BACKGROUND: There are accumulating studies reporting that vitamin E in general exhibits bone protective effects. This systematic review, however discusses the effects of a group of vitamin E isomers, tocotrienols in preventing bone loss through osteoclast differentiation and activity suppression.

    OBJECTIVE: This review is aimed to discuss the literature reporting the effects of tocotrienols on osteoclasts, the cells specialized for resorbing bone.

    RESULTS: Out of the total 22 studies from the literature search, only 11 of them were identified as relevant, which comprised of eight animal studies, two in vitro studies and only one combination of both. The in vivo studies indicated that tocotrienols improve the bone health and reduce bone loss via inhibition of osteoclast formation and resorption activity, which could be through regulation of RANKL and OPG expression as seen from their levels in the sera. This is well supported by data from the in vitro studies demonstrating the suppression of osteoclast formation and resorption activity following treatment with tocotrienol isomers.

    CONCLUSION: Thus, tocotrienols are suggested to be potential antioxidants for prevention and treatment of bone-related diseases characterized by increased bone loss.

  19. Lee SH, Ng CX, Wong SR, Chong PP
    Curr Drug Targets, 2023;24(6):484-508.
    PMID: 36999414 DOI: 10.2174/1389450124666230329123409
    MicroRNAs have a plethora of roles in various biological processes in the cells and most human cancers have been shown to be associated with dysregulation of the expression of miRNA genes. MiRNA biogenesis involves two alternative pathways, the canonical pathway which requires the successful cooperation of various proteins forming the miRNA-inducing silencing complex (miRISC), and the non-canonical pathway, such as the mirtrons, simtrons, or agotrons pathway, which bypasses and deviates from specific steps in the canonical pathway. Mature miRNAs are secreted from cells and circulated in the body bound to argonaute 2 (AGO2) and miRISC or transported in vesicles. These miRNAs may regulate their downstream target genes via positive or negative regulation through different molecular mechanisms. This review focuses on the role and mechanisms of miRNAs in different stages of breast cancer progression, including breast cancer stem cell formation, breast cancer initiation, invasion, and metastasis as well as angiogenesis. The design, chemical modifications, and therapeutic applications of synthetic anti-sense miRNA oligonucleotides and RNA mimics are also discussed in detail. The strategies for systemic delivery and local targeted delivery of the antisense miRNAs encompass the use of polymeric and liposomal nanoparticles, inorganic nanoparticles, extracellular vesicles, as well as viral vectors and viruslike particles (VLPs). Although several miRNAs have been identified as good candidates for the design of antisense and other synthetic modified oligonucleotides in targeting breast cancer, further efforts are still needed to study the most optimal delivery method in order to drive the research beyond preclinical studies.
  20. Kumar D, Sarkar N, Roy KK, Bisht D, Kumar D, Mandal B, et al.
    Curr Drug Targets, 2023;24(8):627-647.
    PMID: 37291783 DOI: 10.2174/1389450124666230608150759
    The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.
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