Displaying publications 1 - 20 of 66 in total

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  1. Teh HX, Phang SJ, Looi ML, Kuppusamy UR, Arumugam B
    Life Sci, 2023 Dec 01;334:122228.
    PMID: 37922981 DOI: 10.1016/j.lfs.2023.122228
    Diabetic wounds are slow healing wounds characterized by disordered healing processes and frequently take longer than three months to heal. One of the defining characteristics of impaired diabetic wound healing is an abnormal and unresolved inflammatory response, which is primarily brought on by abnormal macrophage innate immune signaling activation. The persistent inflammatory state in a diabetic wound may be attributed to inflammatory pathways such as nuclear factor kappa B (NF-ĸB) and nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which have long been associated with inflammatory diseases. Despite the available treatments for diabetic foot ulcers (DFUs) that include debridement, growth factor therapy, and topical anti-bacterial agents, successful wound healing is still hampered. Further understanding of the molecular mechanism of these pathways could be useful in designing potential therapeutic targets for diabetic wound healing. This review provides an update and novel insights into the roles of NF-ĸB and NLRP3 pathways in the molecular mechanism of diabetic wound inflammation and their potential as therapeutic targets in diabetic wound healing.
  2. Mohmad Saberi SE, Chua LS
    Life Sci, 2023 Nov 15;333:122170.
    PMID: 37827234 DOI: 10.1016/j.lfs.2023.122170
    Orthosiphon aristatus has been traditionally used as a medicinal herb for various illnesses in Southeast Asia and Europe. The most dominant bioactive compound of the herb is rosmarinic acid (RosA) which has been demonstrated for its remarkable anti-inflammatory properties. This review describes the recent progress of studies on multi-target molecular pathways of RosA in relation to targeted inflammatory-associated diseases. An inclusive literature search was conducted using electronic databases such as Google Scholar, Scopus, Springer Link, PubMed, Medline, Wiley and Science Direct for studies reporting on the anti-inflammatory actions of RosA from 2008 until 2023. The keywords of the search were RosA and anti-inflammatory in relation to hepatoprotective, chondroprotective, cardioprotective, neuroprotective and toxicity. Only publications that are written in English are included in this review. The inhibition and deactivation of pro-inflammatory biomolecules by RosA were explained based on the initial inflammation stimuli and their location in the body. The activation of Nrf2/HO-1 expression to inhibit NF-κB pathway is the key mechanism for hepatoprotection. Besides NF-κB inhibition, RosA activates PPARγ to alleviate ischemia/reperfusion (I/R)-induced myocardial injury for cardioprotection. The regulation of MAPK and T-cell activation is important for chondroprotection, whereas the anti-oxidant property of RosA is the main contributor of neuroprotection. Even though less studies on the anti-inflammation of RosA extracts from O. aristatus, but the effective pharmacological properties of RosA has promoted it as a natural potent lead for further investigation.
  3. Aamir K, Sethi G, Afrin MR, Hossain CF, Jusuf PR, Sarker SD, et al.
    Life Sci, 2023 Aug 15;327:121856.
    PMID: 37307966 DOI: 10.1016/j.lfs.2023.121856
    BACKGROUND: Arjunolic acid (AA) is a potent phytochemical with multiple therapeutics effects. In this study, AA is evaluated on type 2 diabetic (T2DM) rats to understand the mechanism of β-cell linkage with Toll-like receptor 4 (TLR-4) and canonical Wnt signaling. However, its role in modulating TLR-4 and canonical Wnt/β-catenin crosstalk on insulin signaling remains unclear during T2DM. Aim The current study is aimed to examine the potential role of AA on insulin signaling and TLR-4-Wnt crosstalk in the pancreas of type 2 diabetic rats.

    METHOD: Multiple methods were used to determine molecular cognizance of AA in T2DM rats, when treated with different dosage levels. Histopathological and histomorphometry analysis was conducted using masson trichrome and H&E stains. While, protein and mRNA expressions of TLR-4/Wnt and insulin signaling were assessed using automated Western blotting (jess), immunohistochemistry, and RT-PCR.

    RESULTS: Histopathological findings revealed that AA had reversed back the T2DM-induced apoptosis and necrosis caused to rats pancreas. Molecular findings exhibited prominent effects of AA in downregulating the elevated level of TLR-4, MyD88, NF-κB, p-JNK, and Wnt/β-catenin by blocking TLR-4/MyD88 and canonical Wnt signaling in diabetic pancreas, while IRS-1, PI3K, and pAkt were all upregulated by altering the NF-κB and β-catenin crosstalk during T2DM.

    CONCLUSION: Overall results, indicate that AA has potential to develop as an effective therapeutic in the treatment of T2DM associated meta-inflammation. However, future preclinical research at multiple dose level in a long-term chronic T2DM disease model is warranted to understand its clinical relevance in cardiometabolic disease.

  4. Naeem M, Hazafa A, Bano N, Ali R, Farooq M, Razak SIA, et al.
    Life Sci, 2023 Mar 01;316:121409.
    PMID: 36681183 DOI: 10.1016/j.lfs.2023.121409
    Chimeric antigen receptor (CAR) T therapy has shown remarkable success in discovering novel CAR-T cell products for treating malignancies. Despite of successful results from clinical trials, CAR-T cell therapy is ineffective for long-term disease progression. Numerous challenges of CAR-T cell immunotherapy such as cell dysfunction, cytokine-related toxicities, TGF-β resistance, GvHD risks, antigen escape, restricted trafficking, and tumor cell infiltration still exist that hamper the safety and efficacy of CAR-T cells for malignancies. The accumulated data revealed that these challenges could be overcome with the advanced CRISPR genome editing technology, which is the most promising tool to knockout TRAC and HLA genes, inhibiting the effects of dominant negative receptors (PD-1, TGF-β, and B2M), lowering the risks of cytokine release syndrome (CRS), and regulating CAR-T cell function in the tumor microenvironment (TME). CRISPR technology employs DSB-free genome editing methods that robustly allow efficient and controllable genetic modification. The present review explored the innovative aspects of CRISPR/Cas9 technology for developing next-generation/universal allogeneic CAR-T cells. The present manuscript addressed the ongoing status of clinical trials of CRISPR/Cas9-engineered CAR-T cells against cancer and pointed out the off-target effects associated with CRISPR/Cas9 genome editing. It is concluded that CAR-T cells modified by CRISPR/Cas9 significantly improved antitumor efficacy in a cost-effective manner that provides opportunities for novel cancer immunotherapies.
  5. Pian AK, Foong CP, Hamid RA
    Life Sci, 2022 Dec 15;311(Pt B):121161.
    PMID: 36375571 DOI: 10.1016/j.lfs.2022.121161
    We have previously reported the inhibition of thioredoxin reductase (TrxR) and invasion by tricyclohexylphosphine gold (I) n-mercaptobenzoate (n = 2, 3, 4) labeled as 1-3 towards MCF-7 cells, in vitro. Nevertheless, the mode of death and its apoptotic pathway has yet to be revealed. The main aim of this study is to investigate the anti-neoplastic activity of this phosphanegold (I) thiolates against breast adenocarcinoma cells, MCF-7. Herein, we explored the role of gold(I) series, 1-3 for their apoptosis-inducing ability against MCF-7 cells. They were scrutinized for their antiproliferative activities which exhibited their IC50 values of 8.14 μM ± 0.10, 7.26 μM ± 0.33, and 9.03 μM ± 0.69, respectively, and indicated better cytotoxicities than that of cisplatin (positive control). Further, the mechanisms of their actions were studied by analyzing the status of ROS generation (by DCFH-DA), cytochrome c release (by ELISA), and activation of caspases 3/7, 8, 9, and 10, annexin V staining and cell cycle analysis by flow cytometry, respectively. It was observed that the compounds, 1-3 can promote ROS generation, cytochrome c release, and activation of caspases 3/7, caspase 8, caspase 9, and caspase 10 on MCF-7 cells. In addition, the compounds are shown to induce MCF-7 cell arrest at S-phase. Gene analysis via PCR array further clarified their effects by modulating the related genes upon the compounds' treatment. Further investigation on other breast cancer cells as well as in vivo studies on these compounds will further increase their potential as anti-breast cancer agents.
  6. Tobuse AJ, Ang CW, Yeong KY
    Life Sci, 2022 Aug 01;302:120660.
    PMID: 35642852 DOI: 10.1016/j.lfs.2022.120660
    With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review.
  7. Wang D, Tan KS, Zeng W, Li S, Wang Y, Xu F, et al.
    Life Sci, 2022 Mar 15;293:120336.
    PMID: 35065166 DOI: 10.1016/j.lfs.2022.120336
    AIMS: Individuals with nonalcoholic hepatosteatosis (NAFLD) have a worse atherogenic lipoprotein profile and are susceptible to cardiovascular diseases. The MEK-ERK signaling cascades are central regulators of the levels of LDL receptor (LDLR), a major determinant of circulating cholesterol. It is elusive how hepatic steatosis contributes to dyslipidemia, especially hypercholesterolemia.

    MAIN METHODS: The effects of BChE on signaling pathways were determined by immunoblotting in a BChE knockout hepatocyte cell line. DiI-LDL probe was used to explore the effect of BChE expression on LDL internalization. Co-immunoprecipitation and LC-MS were used to explore the interacting proteins with BChE. Finally, a hepatocyte-restricted BChE silencing mouse model was established by AAV8-Tbg-shRNA, and the hypercholesterolemia was induced by 65% kcal% high-fat, high-sucrose diet feeding.

    MAIN FINDINGS: Here we demonstrate that butyrylcholinesterase (BChE) governs the LDL receptor levels and LDL uptake capacity through the MEK-ERK signaling cascades to promote Ldlr transcription. BChE interacts and co-localizes with PRMT5, a protein methylation modifier controlling the ERK signaling. PRMT5 regulates LDLR-dependent LDL uptake and is a substrate of chaperone-mediated autophagy (CMA). BChE deficiency induces the PRTM5 degradation dependent on CMA activity, possibly through facilitating the HSC70 (Heat shock cognate 71 kDa) recognition of PRMT5. Remarkably, in vivo hepatocyte-restricted BChE silencing reduces plasma cholesterol levels substantially. In contrast, the BChE knockout mice are predisposed to hypercholesterolemia.

    SIGNIFICANCE: Taken together, these findings outline a regulatory role for the BChE-PRMT5-ERK-LDLR axis in hepatocyte cholesterol metabolism, and suggest that targeting liver BChE is an effective therapeutic strategy to treat hypercholesterolemia.

  8. Aamir K, Khan HU, Hossain CF, Afrin MR, Jusuf PR, Waheed I, et al.
    Life Sci, 2022 Jan 15;289:120232.
    PMID: 34919901 DOI: 10.1016/j.lfs.2021.120232
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide health issue primarily due to failure of pancreatic β-cells to release sufficient insulin.

    PURPOSE: The present work aimed to assess the antidiabetic potential of arjunolic acid (AA) isolated from Terminalia arjuna in type 2 diabetic rats.

    STUDY DESIGN: After extraction, isolation and purification, AA was orally administered to type 2 diabetic Sprague Dawley rats to investigate antidiabetic effect of AA.

    METHOD: T2DM was induced via single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NIC) in adult male rats. After 10 days, fasting and random blood glucose (FBG and RBG), body weight (BW), food and water intake, serum C-peptide, insulin and glycated hemoglobin (HbA1c) was measured to confirm T2DM development. Dose dependent effects of orally administered AA (25 and 50 mg/kg/day) for 4 weeks was investigated by measuring BW variation, fasting and postprandial hyperglycemia, oral glucose tolerance test (OGTT), and levels of serum HbA1c, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), serum and pancreatic C-peptide, insulin, growth differentiation factor 15 (GDF-15), serum and pancreatic inflammatory cytokines.

    RESULTS: The oral administration of AA in preclinical model of T2DM significantly normalized FBG and RBG, restored BW, controlled polyphagia, polydipsia and glucose tolerance. In addition, AA notably reduced serum HbA1c, TC, TG, LDL with non-significant increase in HDL. On the other hand, significant increase in serum and pancreatic C-peptide and insulin was observed with AA treatment, while serum and pancreatic GDF-15 were non-significantly altered in AA treated diabetic rats. Moreover, AA showed dose dependent reduction in serum and pancreatic proinflammatory cytokines including TNF-α, IL-1β and IL-6.

    CONCLUSION: For the first time our findings highlighted AA as a potential candidate in type 2 diabetic conditions.

  9. Sudhakaran G, Guru A, Hari Deva Muthu B, Murugan R, Arshad A, Arockiaraj J
    Life Sci, 2022 Jan 03;291:120276.
    PMID: 34990650 DOI: 10.1016/j.lfs.2021.120276
    Polycystic ovarian syndrome (PCOS) causes swollen ovaries in women at reproductive age due to hormonal disorder with small cysts on the outer edges. The cause of the disorder is still yet to be found. Multiple factors have increased PCOS prevalence, hyperandrogenism, oxidative stress, inflammation, and insulin resistance. Various animal PCOS models have been developed to imitate the pathophysiology of PCOS in humans. Zebrafish is one of the most versatile animal experimental models because of the transparency of the embryos, small size, and rapid growth. The zebrafish similarity to higher vertebrates made it a useful non-mammalian model for PCOS drug testing and screening. This review provides an insight into the usage of zebrafish, a non-mammalian model for PCOS, as an opportunity for evaluating future initiatives in such a research domain.
  10. Lalani S, Tan SH, Tan KO, Lim HX, Ong KC, Wong KT, et al.
    Life Sci, 2021 Dec 15;287:120097.
    PMID: 34715144 DOI: 10.1016/j.lfs.2021.120097
    AIMS: Enterovirus A71 (EV-A71) is an etiological agent of hand foot and mouth disease (HFMD) and has the potential to cause severe neurological infections in children. L-SP40 peptide was previously known to inhibit EV-A71 by prophylactic action. This study aimed to identify the mechanism of inhibition in Rhabdomyosarcoma (RD) cells and in vivo therapeutic potential of L-SP40 peptide in a murine model.

    MAIN METHODS: A pull-down assay was performed to identify the binding partner of the L-SP40 peptide. Co-immunoprecipitation and co-localization assays with the L-SP40 peptide were employed to confirm the receptor partner in RD cells. The outcomes were validated using receptor knockdown and antibody blocking assays. The L-SP40 peptide was further evaluated for the protection of neonatal mice against lethal challenge by mouse-adapted EV-A71.

    KEY FINDINGS: The L-SP40 peptide was found to interact and co-localize with nucleolin, the key attachment receptor of Enteroviruses A species, as demonstrated in the pull-down, co-immunoprecipitation and co-localization assays. Knockdown of nucleolin from RD cells led to a significant reduction of 3.5 logs of viral titer of EV-A71. The L-SP40 peptide demonstrated 80% protection of neonatal mice against lethal challenge by the mouse-adapted virus with a drastic reduction in the viral loads in the blood (~4.5 logs), skeletal muscles (1.5 logs) and brain stem (1.5 logs).

    SIGNIFICANCE: L-SP40 peptide prevented severe hind limb paralysis and death in suckling mice and could serve as a potential broad-spectrum antiviral candidate to be further evaluated for safety and potency in future clinical trials against EV-A71.

  11. Vyas T, Rapalli VK, Chellappan DK, Dua K, Dubey SK, Singhvi G
    Life Sci, 2021 Dec 15;287:120148.
    PMID: 34785190 DOI: 10.1016/j.lfs.2021.120148
    BACKGROUND: Biofilms are microcolonies of microbes that form communities with a variety of microbes, exhibit the same gene composition but differ in gene expression. Biofilm-associated infections have been in existence for a long, however, biofilm-associated skin disorders have not been investigated much.

    OBJECTIVES: Biofilms, which are made mostly of the matrix can be thought of as communities of microbes that are more virulent and more difficult to eradicate as compared to their planktonic counterparts. Currently, several formulations are available in the market which have the potential to treat biofilm-assisted skin disorders. However, the existing pharmacotherapies are not competent enough to cure them effectively and entirely, in several cases.

    KEY FINDINGS: Especially with the rising resistance towards antibiotics, it has become particularly challenging to ameliorate these disorders completely. The new approaches are being used to combat biofilm-associated skin disorders, some of them being photodynamic therapy, nanotherapies, and the use of novel drug delivery systems. The focus of attention, however, is nanotherapy. Micelles, solid lipid nanoparticles, quatsomes, and many others are being considered to find a better solution for the biofilm-associated skin disorders.

    SIGNIFICANCE: This review is an attempt to give a perspective on these new approaches for treating bacterial biofilms associated with skin disorders.

  12. Vendidandala NR, Yin TP, Nelli G, Pasupuleti VR, Nyamathulla S, Mokhtar SI
    Life Sci, 2021 Dec 01;286:120019.
    PMID: 34624322 DOI: 10.1016/j.lfs.2021.120019
    This study is designed to investigate the combination of gallocatechin (GC) and silver nanoparticles (AgNPs) for its wound healing ability in diabetic rats. Thirty male Sprague Dawley rats were randomly divided into 5 groups: 1. Normal control rats dressed with blank CGP1; 2. Diabetic rats dressed with blank CGP1; 3. Diabetic rats dressed with 13.06μM of GC; 4. Diabetic rats dressed with 26.12 μM of GC; 5. Diabetic rats dressed with 0.1% silver sulfadiazine patches. GC-AgNPs-CGP dressed diabetic rats showed significant FBG reduction, prevented the body weight losses and reduced the oxidative stress by lowering MDA content and elevated antioxidant enzymes such as SOD, CAT and GPx in wound healing skin of diabetic rats when compared to normal CGP. Besides, mRNA expression of Nrf2, Nqo-1, and Ho-1 was upregulated with downregulated expression of Keap-1 mRNA, which is supported by immunohistochemistry. Furthermore, GC-AgNPs-CGP dressing increased growth factors such as VEGF, EGF, TGF-β, and FGF-2 while decreasing MMP-2 in the skin of diabetic wound rats. In vitro permeation study demonstrated rapid GC release and permeation with a flux of 0.061 and 0.143 mg/sq.cm/h. In conclusion, the results indicated that GC-AgNPs-CGP dressing on diabetic wound rats modulated oxidative stress and inflammation with elevated growth factors; increased collagen synthesis thereby significantly improved the wound healing and could be beneficial for the management of diabetic wounds.
  13. Ahmad S, Hatmal MM, Lambuk L, Al-Hatamleh MAI, Alshaer W, Mohamud R
    Life Sci, 2021 Dec 01;286:120063.
    PMID: 34673116 DOI: 10.1016/j.lfs.2021.120063
    COVID-19 is a multi-faceted disease ranging from asymptomatic to severely ill condition that primarily affects the lungs and could advance to other organs as well. It's causing factor, SARS-CoV-2 is recognized to develop robust cell-mediated immunity that responsible to either control or exaggerate the infection. As an important cell subset that control immune responses and are significantly dysregulated in COVID-19, Tregs is proposed to be considered for COVID-19 management. Among its hallmark, TNFR2 is recently recognized to play important role in the function and survival of Tregs. This review gathers available TNFR2 agonists to directly target Tregs as a potential approach to overcome immune dysregulation that affect the severity in COVID-19. Furthermore, this review performs a rigid body docking of TNF-TNFR2 interaction and such interaction with TNFR2 agonist to predict the optimal targeting approach.
  14. Zhang GH, Pare RB, Chin KL, Qian YH
    Life Sci, 2021 Nov 25.
    PMID: 34838849 DOI: 10.1016/j.lfs.2021.120178
    AIMS: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder seriously endangering the physical and mental health of the elderly, while no effective treatments and drugs in clinical practice are available. Thymosin β4 (Tβ4) is a multifunctional polypeptide involved in many physiological and pathological processes including AD. This study aims to understand the function and molecular mechanism of Tβ4 in the development of AD.

    MAIN METHODS: Neuroblastoma cell line SH-SY5Y was treated with β-amyloid (Aβ) to induce AD-like pathological changes, which serves as Alzheimer's disease model. Tβ4 was overexpressed in SH-SY5Y cells by lentivirus infection, and downregulated by siRNA transfection. Apoptosis of transfected SH-SY5Y cells after Aβ-treatment was examined by western blot and flow cytometry. Apoptotic proteins and Tβ4-related signaling pathways were also investigated by western blot.

    KEY FINDINGS: We found that Tβ4 overexpression increased viability and suppressed apoptosis of Aβ-treated SH-SY5Y cells. Tβ4 ameliorated oxidative damage and suppressed reactive oxygen species production in Aβ-treated SH-SY5Y cells. Consistently, Tβ4 overexpression down-regulated the expression levels of pro-apoptotic markers such as Caspase-3, Caspase-8, and Bax, while up-regulated the expression level of anti-apoptotic gene Bcl-2 in Aβ-stimulated SH-SY5Y cells. Mechanistically, we demonstrated that Tβ4 dampened ERK/p38 MAPK signaling and enhanced 5-HTR1A expression in Aβ-treated SH-SY5Y cells. Moreover, we revealed that Tβ4 inhibited the activation of ERK pathway through up-regulating 5-HTR1A in Aβ-treated SH-SY5Y cells.

    SIGNIFICANCE: Taken together, our findings provide evidences to support the neuroprotective role of Tβ4 and might open up new therapeutic applications of Tβ4 in AD treatment.

  15. Gulati N, Chellappan DK, MacLoughlin R, Dua K, Dureja H
    Life Sci, 2021 Nov 15;285:119969.
    PMID: 34547339 DOI: 10.1016/j.lfs.2021.119969
    Inflammatory lung diseases related morbidity and mortality impose a significant financial burden. Inflammation is a hallmark of many diseases of the respiratory system which is directly or indirectly linked to adverse health conditions, air pollution, rapid lifestyle changes, and regular outbreaks of microbial infections. The unique anatomical and physiological features of the lungs make them an ideal target organ in the treatment of inflammatory respiratory disease and with the help of inhaled therapy lungs can be targeted directly. The principal objective of this review is to present the comprehensive role of inhaled nano-based therapeutics such as liposomes, niosomes, nanoparticles, nanoemulsion, nanosuspension, and exosomes in the treatment and management of inflammatory respiratory diseases. Inhaled nanomedicines provide targeted diagnosis and treatment, improved drug solubility and distribution, prevent first-pass hepatic metabolism, improved patient compliance, and reduced drug side effects. They overcome several biological barriers in the human body and provide immediate, and quick-onset of action. Future research should be focused on improving the therapeutic efficiency of inhaled nanocarriers and to carry out in-depth mechanistic studies to translate current scientific knowledge for the efficient management of inflammatory lung diseases with minimal or no toxicity.
  16. Phua CYH, Teoh ZL, Goh BH, Yap WH, Tang YQ
    Life Sci, 2021 Nov 08;287:120120.
    PMID: 34762903 DOI: 10.1016/j.lfs.2021.120120
    Cancer is a heterogeneous disease with high morbidity and mortality rate involving changes in redox balance and deregulation of redox signalling. For decades, studies have involved developing an effective cancer treatment to combat treatment resistance. As natural products such as thymoquinone have numerous health benefits, studies are also focusing on using them as a viable method for cancer treatment, as they have minimal toxic effects compared with standard cancer treatments. Thymoquinone studies have shown numerous mechanisms of action, such as regulation of reactive species interfering with DNA structure, modulating various potential targets and their signalling pathways as well as immunomodulatory effects in vitro and in vivo. Thymoquinone's anti-cancer effect is mainly due to the induction of apoptotic mechanisms, such as activation of caspases, downregulation of precancerous genes, inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), anti-tumour cell proliferation, ROS regulation, hypoxia and anti-metastasis. Insight into thymoquinone's potential as an alternative treatment for chemoprevention and inflammation can be accomplished via compiling these studies, to provide a better understanding on how and why it works, as well as its interactions with common chemotherapeutic treatments.
  17. Tan YJ, Lee YT, Mancera RL, Oon CE
    Life Sci, 2021 Nov 01;284:119747.
    PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747
    BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.
  18. Shastri MD, Allam VSRR, Shukla SD, Jha NK, Paudel KR, Peterson GM, et al.
    Life Sci, 2021 Oct 15;283:119871.
    PMID: 34352260 DOI: 10.1016/j.lfs.2021.119871
    Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.
  19. Corrie L, Gulati M, Singh SK, Kapoor B, Khursheed R, Awasthi A, et al.
    Life Sci, 2021 Sep 01;280:119753.
    PMID: 34171379 DOI: 10.1016/j.lfs.2021.119753
    Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.
  20. Chan Y, Ng SW, Singh SK, Gulati M, Gupta G, Chaudhary SK, et al.
    Life Sci, 2021 Sep 01;280:119744.
    PMID: 34174324 DOI: 10.1016/j.lfs.2021.119744
    Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.
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