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  1. Dua K, Sheshala R, Al-Waeli HA, Gupta G, Chellappan DK
    Recent Pat Drug Deliv Formul, 2015;9(3):257-61.
    PMID: 26051152
    Natural products like plants and its components have been in use for treatment and cure of diseases all around the globe from ancient times much before the discovery of the current modern drugs. These substances from the nature are well known to contain components which have therapeutic properties and can also behave as precursors for the synthesis of potential drugs. The beneficial results from herbal drugs are well reported where their popularity in usage has increased across the globe. Subsequently developing countries are now recognizing the many positive advantages from their use which has engaged the expansion of R & D from herbal research. The flow on effect from this expansion has increased the awareness to develop new herbal products and the processes, throughout the entire world. Mouth washes and mouth rinses which have plant oils, plant components or extracts have generated particular attention. High prevalence of gingival inflammation and periodontal diseases, suggests majority of the patients practice inadequate plaque control. Of the currently available mouthwashes in the market, Chlorhexidine gluconate (CHX) has been investigated on a larger scale with much detail. CHX is associated with side effects like staining of teeth when used daily as well as the bitter taste of the mouthwash which leads to patient incompliance. The present research encompasses the antibacterial activity of extemporaneously prepared herbal mouthwash using natural herbs and therefore allows for the potential commercialization with in the herbal and pharmaceutical industries. Also, the present research article reviewed details of various existing patents of herbal mouthwashes which shows the trend of existing market and significance of emerging mouthwashes in both pharmaceutical and herbal industries. The antimicrobial activity of prepared mouthwashes was found to be effective against various strains of bacteria. It also suggests that the prepared herbal mouthwashes may provide an alternative to those containing chemical entities, with enhanced antimicrobial properties and better patient compliance.
  2. Sheshala R, Kok YY, Ng JM, Thakur RR, Dua K
    Recent Pat Drug Deliv Formul, 2015;9(3):237-48.
    PMID: 26205681
    Ophthalmic drug delivery system is very interesting and challenging due to the normal physiologically factor of eyes which reduces the bioavailability of ocular products. The development of new ophthalmic dosage forms for existing drugs to improve efficacy and bioavailability, patient compliance and convenience has become one of the main trend in the pharmaceuticals industry. The present review encompasses various conventional and novel ocular drug delivery systems, methods of preparation, characterization and recent research in this area. Furthermore, the information on various commercially available in situ gel preparations and the existing patents of in situ drug delivery systems i.e. in situ gel formation of pectin, in situ gel for therapeutic use, medical uses of in situ formed gels and in situ gelling systems as sustained delivery for front of eye are also covered in this review.
  3. Jamil K, Chua KH, Joudi S, Ng SL, Yahaya NH
    J Orthop Surg Res, 2015;10:27.
    PMID: 25889942 DOI: 10.1186/s13018-015-0166-z
    Functional tissue engineering has emerged as a potential means for treatment of cartilage defect. Development of a stable cartilage composite is considered to be a good option. The aim of the study was to observe whether the incorporation of cultured chondrocytes on porous tantalum utilizing fibrin as a cell carrier would promote cartilage tissue formation.
  4. Zakaria N, Yusoff NM, Zakaria Z, Lim MN, Baharuddin PJ, Fakiruddin KS, et al.
    BMC Cancer, 2015;15:84.
    PMID: 25881239 DOI: 10.1186/s12885-015-1086-3
    Despite significant advances in staging and therapies, lung cancer remains a major cause of cancer-related lethality due to its high incidence and recurrence. Clearly, a novel approach is required to develop new therapies to treat this devastating disease. Recent evidence indicates that tumours contain a small population of cells known as cancer stem cells (CSCs) that are responsible for tumour maintenance, spreading and resistant to chemotherapy. The genetic composition of CSCs so far is not fully understood, but manipulation of the specific genes that maintain their integrity would be beneficial for developing strategies to combat cancer. Therefore, the goal of this study isto identify the transcriptomic composition and biological functions of CSCs from non-small cell lung cancer (NSCLC).
  5. Satija S, Mehta M, Sharma M, Prasher P, Gupta G, Chellappan DK, et al.
    Future Med Chem, 2020 09;12(18):1607-1609.
    PMID: 32589055 DOI: 10.4155/fmc-2020-0149
  6. Shah K, Arfan M, Mahariq I, Ahmadian A, Salahshour S, Ferrara M
    Results Phys, 2020 Dec;19:103560.
    PMID: 33200064 DOI: 10.1016/j.rinp.2020.103560
    This work is the consideration of a fractal fractional mathematical model on the transmission and control of corona virus (COVID-19), in which the total population of an infected area is divided into susceptible, infected and recovered classes. We consider a fractal-fractional order

    SIR

    type model for investigation of Covid-19. To realize the transmission and control of corona virus in a much better way, first we study the stability of the corresponding deterministic model using next generation matrix along with basic reproduction number. After this, we study the qualitative analysis using "fixed point theory" approach. Next, we use fractional Adams-Bashforth approach for investigation of approximate solution to the considered model. At the end numerical simulation are been given by matlab to provide the validity of mathematical system having the arbitrary order and fractal dimension.
  7. Zainudin MHM, Mustapha NA, Hassan MA, Bahrin EK, Tokura M, Yasueda H, et al.
    Sci Rep, 2019 09 19;9(1):13526.
    PMID: 31537863 DOI: 10.1038/s41598-019-50126-y
    A thermophilic Thermobifida fusca strain UPMC 901, harboring highly thermostable cellulolytic activity, was successfully isolated from oil palm empty fruit bunch compost. Its endoglucanase had the highest activity at 24 hours of incubation in carboxymethyl-cellulose (CMC) and filter paper. A maximum endoglucanase activity of 0.9 U/mL was achieved at pH 5 and 60 °C using CMC as a carbon source. The endoglucanase properties were further characterized using crude enzyme preparations from the culture supernatant. Thermal stability indicated that the endoglucanase activity was highly stable at 70 °C for 24 hours. Furthermore, the activity was found to be completely maintained without any loss at 50 °C and 60 °C for 144 hours, making it the most stable than other endoglucanases reported in the literature. The high stability of the endoglucanase at an elevated temperature for a prolonged period of time makes it a suitable candidate for the biorefinery application.
  8. Masran R, Zanirun Z, Bahrin EK, Ibrahim MF, Lai Yee P, Abd-Aziz S
    Appl Microbiol Biotechnol, 2016 Jun;100(12):5231-46.
    PMID: 27115758 DOI: 10.1007/s00253-016-7545-1
    Abundant lignocellulosic biomass from various industries provides a great potential feedstock for the production of value-added products such as biofuel, animal feed, and paper pulping. However, low yield of sugar obtained from lignocellulosic hydrolysate is usually due to the presence of lignin that acts as a protective barrier for cellulose and thus restricts the accessibility of the enzyme to work on the cellulosic component. This review focuses on the significance of biological pretreatment specifically using ligninolytic enzymes as an alternative method apart from the conventional physical and chemical pretreatment. Different modes of biological pretreatment are discussed in this paper which is based on (i) fungal pretreatment where fungi mycelia colonise and directly attack the substrate by releasing ligninolytic enzymes and (ii) enzymatic pretreatment using ligninolytic enzymes to counter the drawbacks of fungal pretreatment. This review also discusses the important factors of biological pretreatment using ligninolytic enzymes such as nature of the lignocellulosic biomass, pH, temperature, presence of mediator, oxygen, and surfactant during the biodelignification process.
  9. Singh Y, Gupta G, Kazmi I, Al-Abbasi FA, Negi P, Chellappan DK, et al.
    Dermatol Ther, 2020 11;33(6):e13871.
    PMID: 32558055 DOI: 10.1111/dth.13871
    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the primary causative organism in corona virus disease-19 (COVID-19) infections, is a novel member of the human coronavirus family which was first identified in Wuhan, China, towards the end of 2019. This letter reveals new vital missing links in our current understanding of the mechanisms that lead to cell death triggered by ferroptotic stress in COVID-19 infection. It further reveal the importance of homocysteine mediated trans-sulfuration pathway in COVID-19 infection. Hence, Vitamin B6, folic acid, and Vitamin B12 should be incorporated in the treatment regimen for SARS CoV-2 infections to suppress complications, as the virus mediates altered host cell metabolism.
  10. Pandey P, Chellappan DK, Tambuwala MM, Bakshi HA, Dua K, Dureja H
    Int J Biol Macromol, 2019 Dec 01;141:596-610.
    PMID: 31494160 DOI: 10.1016/j.ijbiomac.2019.09.023
    The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer.
  11. Chellappan DK, Yap WS, Bt Ahmad Suhaimi NA, Gupta G, Dua K
    Panminerva Med, 2018 Sep;60(3):117-131.
    PMID: 29696964 DOI: 10.23736/S0031-0808.18.03455-9
    The prevalence of type 2 diabetes mellitus (T2DM) has been increasing at an alarming rate. With an increased understanding of the pathophysiology and pathogenesis of T2DM, various new therapeutic options have been developed to target different key defects in T2DM. Incremental innovations of existing therapies either through unprecedented drug combinations, modified drug molecules, or improved delivery systems are capable to nullify some of the undesirable side effects of traditional therapies as well as to enhance effectiveness. The existing administration routes include inhalation, nasal, buccal, parenteral and oral. Newer drug targets such as protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), sirtuin (SIRT), and others are novel approaches that act via different mechanisms and possibly treating T2DM of distinct variations and aetiologies. Other therapies such as endobarrier, gene therapy, and stem cell technology utilize advanced techniques to treat T2DM, and the potential of these therapies are still being explored. Gene therapy is plausible to fix the underlying pathology of T2DM instead of using traditional reactive treatments, especially with the debut of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein9 (CRISPR-Cas9) gene editing tool. Molecular targets in T2DM are also being extensively studied as it could target the defects at the molecular level. Furthermore, antibody therapies and vaccinations are also being developed against T2DM; but the ongoing clinical trials are relatively lesser and the developmental progress is slower. Although, there are many therapies designed to cure T2DM, each of them has their own advantages and disadvantages. The preference for the treatment plan usually depends on the health status of the patient and the treatment goal. Therefore, an ideal treatment should take patient's compliance, efficacy, potency, bioavailability, and other pharmacological and non-pharmacological properties into account.
  12. Rajan R, Sam-Aan M, Kosai NR, Shuhaili MA, Chee TS, Venkateswaran A, et al.
    J Minim Access Surg, 2019 1 9;16(1):47-53.
    PMID: 30618425 DOI: 10.4103/jmas.JMAS_219_18
    Introduction: Despite many challenges, the benefit of bariatric surgery in super-obese population remains irrefutable with significant improvement in metabolic syndrome and quality of life. There are currently no published data from Malaysia on this topic.

    Objective and Methodology: A single-centre retrospective study aimed at analysing the outcome of laparoscopic bariatric surgery on super-obese Malaysians with type 2 diabetes mellitus (T2DM) at 12 months following surgery. Demographic details, glycaemic control and weight-loss parameters were analysed.P < 0.01 was considered statistically significant.

    Results: Of the 33 patients, 55% were women and 45% were men with a mean age of 40 ± 11 years and body mass index (BMI) of 59.3 ± 9.0 kg/m2. Majority of patients were of Malay ethnicity (82%). Malaysian-Indians and Malaysian-Chinese each accounted for 9% of total case volume. The three types of laparoscopic bariatric surgery recorded in this study were sleeve gastrectomy (82%), Roux-en-Y gastric bypass (9%) and mini-gastric bypass (9%) with operative time of 103.5 ± 31.1, 135.8 ± 32.6 and 116.2 ± 32.3 min, respectively. Percentage total body weight loss was 33.11% ± 9.44% at 12 months following surgery (P < 0.01). BMI change and percentage excess BMI loss showed similar improvement. Glycosylated haemoglobin and fasting blood sugar decreased from pre-operative values of 7.0% ± 1.0% and 7.0 ± 0.9 mmol/L to 5.6% ± 0.4% and 5.0 ± 0.6 mmol/L at 12 months (P < 0.01). Remission of T2DM was noted in 93% of patients. There was no correlation between weight loss and improvement in glycaemic status.

    Conclusion: There are significant weight loss and improvement of glycaemic control at 12 months post-laparoscopic bariatric surgery among super-obese Malaysians.

  13. Fakiruddin KS, Lim MN, Nordin N, Rosli R, Zakaria Z, Abdullah S
    Cancers (Basel), 2019 08 28;11(9).
    PMID: 31466290 DOI: 10.3390/cancers11091261
    Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.
  14. Dua K, Chellappan DK, Singhvi G, de Jesus Andreoli Pinto T, Gupta G, Hansbro PM
    Panminerva Med, 2018 Dec;60(4):230-231.
    PMID: 30563304 DOI: 10.23736/S0031-0808.18.03459-6
  15. Sunkara K, Allam VR, Shukla SD, Chellappan DK, Gupta G, MacLoughlin R, et al.
    EXCLI J, 2021;20:248-251.
    PMID: 33628161 DOI: 10.17179/excli2021-3322
  16. Ali ME, Hashim U, Mustafa S, Che Man YB, Dhahi TS, Kashif M, et al.
    Meat Sci, 2012 Aug;91(4):454-9.
    PMID: 22444666 DOI: 10.1016/j.meatsci.2012.02.031
    A test for assessing pork adulteration in meatballs, using TaqMan probe real-time polymerase chain reaction, was developed. The assay combined porcine-specific primers and TaqMan probe for the detection of a 109 bp fragment of porcine cytochrome b gene. Specificity test with 10 ng DNA of eleven different species yielded a threshold cycle (Ct) of 15.5 ± 0.20 for the pork and negative results for the others. Analysis of beef meatballs with spiked pork showed the assay can determine 100-0.01% contaminated pork with 102% PCR efficiency, high linear regression (r(2) = 0.994) and ≤ 6% relative errors. Residuals analysis revealed a high precision in all determinations. Random analysis of commercial meatballs from pork, beef, chicken, mutton and goat, yielded a Ct between 15.89 ± 0.16 and 16.37 ± 0.22 from pork meatballs and negative results from the others, showing the suitability of the assay to determine pork in commercial meatballs with a high accuracy and precision.
  17. Raychaudhuri R, Pandey A, Hegde A, Abdul Fayaz SM, Chellappan DK, Dua K, et al.
    Expert Opin Drug Deliv, 2020 12;17(12):1737-1765.
    PMID: 32878492 DOI: 10.1080/17425247.2020.1819237
    Introduction: In this review, we aim to highlight the impact of various processes and formulation variables influencing the characteristics of certain surfactant-based nanoconstructs for drug delivery. Areas covered: The review includes the discussion on processing parameters for the preparation of nanoconstructs, especially those made up of surfactants. Articles published in last 15 years (437) were reviewed, 381 articles were selected for data review and most appropriate articles (215) were included in article. Effect of variables such as surfactant concentration and type, membrane additives, temperature, and pH-dependent transitions on morphology has been highlighted along with effect of shape on nanoparticle uptake by cells. Various characterization techniques explored for these nanostructures with respect to size, morphology, lamellarity, distribution, etc., and a separate section on polymeric vesicles and the influence of block copolymers, type of block copolymer, control of block length, interaction of multiple block copolymers on the structure of polymersomes and chimeric nanostructures have been discussed. Finally, applications, modification, degradation, and toxicological aspects of these drug delivery systems have been highlighted. Expert opinion: Parameters influencing the morphology of micelles and vesicles can directly or indirectly affect the efficacy of small molecule cellular internalization as well as uptake in the case of biologicals.[Figure: see text].
  18. Sharip NS, Ariffin H, Andou Y, Shirosaki Y, Bahrin EK, Jawaid M, et al.
    Molecules, 2020 Sep 30;25(19).
    PMID: 33008017 DOI: 10.3390/molecules25194498
    Incorporation of nanocellulose could improve wear resistance of ultra-high molecular weight polyethylene (UHMWPE) for an artificial joint application. Yet, the extremely high melt viscosity of the polymer may constrict the mixing, leading to fillers agglomeration and poor mechanical properties. This study optimized the processing condition of UHMWPE/cellulose nanofiber (CNF) bionanocomposite fabrication in triple screw kneading extruder by using response surface methodology (RSM). The effect of the process parameters-temperature (150-190 °C), rotational speed (30-60 rpm), and mixing time (30-45 min)-on mechanical properties of the bionanocomposites was investigated. Homogenous filler distribution, as confirmed by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) analysis, was obtained through the optimal processing condition of 150 °C, 60 rpm, and 45 min. The UHMWPE/CNF bionanocomposites exhibited improved mechanical properties in terms of Young's and flexural modulus by 11% and 19%, respectively, as compared to neat UHMWPE. An insignificant effect was observed when maleic anhydride-grafted-polyethylene (MAPE) was added as compatibilizer. The obtained results proved that homogenous compounding of high melt viscosity UHMWPE with CNF was feasible by optimizing the melt blending processing condition in triple screw kneading extruder, which resulted in improved stiffness, a contributing factor for wear resistance.
  19. Adil MT, Aminian A, Bhasker AG, Rajan R, Corcelles R, Zerrweck C, et al.
    Obes Surg, 2020 02;30(2):483-492.
    PMID: 31677017 DOI: 10.1007/s11695-019-04195-7
    BACKGROUND: Sleeve Gastrectomy (SG) is the most commonly performed bariatric procedure worldwide. There is currently no scientific study aimed at understanding variations in practices concerning this procedure. The aim of this study was to study the global variations in perioperative practices concerning SG.

    METHODS: A 37-item questionnaire-based survey was conducted to capture the perioperative practices of the global community of bariatric surgeons. Data were analyzed using descriptive statistics.

    RESULTS: Response of 863 bariatric surgeons from 67 countries with a cumulative experience of 520,230 SGs were recorded. A total of 689 (80%) and 764 (89%) surgeons listed 13 absolute and relative contraindications, respectively. 65% (n = 559) surgeons perform routine preoperative endoscopy and 97% (n = 835) routinely use intraoperative orogastric tube for sizing the resection. A wide variation is observed in the diameter of the tube used. 73% (n = 627) surgeons start dividing the stomach at a distance of 3-5 cm from the pylorus, and 54% (n = 467) routinely use staple line reinforcement. Majority (65%, n = 565) of surgeons perform routine intraoperative leak test at the end of the procedure, while 25% (n = 218) surgeons perform a routine contrast study in the early postoperative period. Lifelong multivitamin/mineral, iron, vitamin D, calcium, and vitamin B12 supplementation is advocated by 66%, 29%, 40%, 38% and 44% surgeons, respectively.

    CONCLUSION: There is a considerable variation in the perioperative practices concerning SG. Data can help in identifying areas for future consensus building and more focussed studies.

  20. Ramos AC, Chevallier JM, Mahawar K, Brown W, Kow L, White KP, et al.
    Obes Surg, 2020 May;30(5):1625-1634.
    PMID: 32152841 DOI: 10.1007/s11695-020-04519-y
    BACKGROUND: One-anastomosis gastric bypass (OAGB-MGB) is currently the third performed primary bariatric surgical procedure worldwide. However, the procedure is hampered by numerous controversies and there is considerable variability in surgical technique, patient selection, and pre- and postoperative care among the surgeons performing this procedure. This paper reports the results of a modified Delphi consensus study organized by the International Federation for Surgery of Obesity and Metabolic Disorders (IFSO).

    METHODS: Fifty-two internationally recognized bariatric experts from 28 countries convened for voting on 90 consensus statements over two rounds to identify those on which consensus could be reached. Inter-voter agreement of ≥ 70% was considered consensus, with voting participation ≥ 80% considered a robust vote.

    RESULTS: At least 70% consensus was achieved for 65 of the 90 questions (72.2% of the items), 61 during the first round of voting and an additional four in the second round. Where consensus was reached on a binary agree/disagree or yes/no item, there was agreement with the statement presented in 53 of 56 instances (94.6%). Where consensus was reached on a statement where options favorable versus unfavorable to OAGB-MGB were provided, including statements in which OAGB-MGB was compared to another procedure, the response option favorable to OAGB-MGB was selected in 13 of 23 instances (56.5%).

    CONCLUSION: Although there is general agreement that the OAGB-MGB is an effective and usually safe option for the management of patients with obesity or severe obesity, numerous areas of non-consensus remain in its use. Further empirical data are needed.

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